Well, good morning, good afternoon, good evening, everyone. Welcome back to day three, IGCS 2021 Annual Global Meeting. We begin today with an exciting kind of event. This is our award ceremony, where we'll be honoring 12 inspiring and distinguished individuals in one organization. You know, it's so important that we take time to acknowledge those who are doing exceptional work in the global gynecologic cancer community. Their commitment and contributions inspire future generations and really show us what is possible. IGCS now has six different award categories. The Lifetime Achievement Award, the Award for Outstanding Achievement in Gynecologic Oncology Surgery, the Global Humanitarian Award, the Excellence in Teaching Award, the Award for Community Advancement in Resource-Limited Settings, and the Distinguished Advocacy Award. The 2021 award recipients were announced in July. You can read more about each of them in the program book or on the IGCS website. Now we will hear from each of them and play their prerecorded acceptance speeches. The first is Dr. Beth Carlin, receiving the Lifetime Achievement Award. Hello and good day from Los Angeles, California. I'm sorry I can't be there with you for this very special IGCS meeting. Rome is one of my favorite cities and IGCS is one of my favorite scientific meetings. It's just that my son's wedding celebration had to be my priority today. Let me start by thanking Dr. Coleman and the IGCS board for distinguishing me with their prestigious Lifetime Achievement Award. I'm humbled by this recognition and especially honored to be receiving this award along with my esteemed colleagues from around the globe. Each of you have demonstrated leadership and dedication to our specialty and have been exemplars for a generation of gynecologic oncologists. Salute and congratulations to all of you. Most days I wake up with an urgency to make the world a better place. Helping the world is my primary goal. Helping women with gynecologic malignancies to live longer and better lives has not only been my lifelong commitment, but this quest has greatly enriched my own life. The physician-patient relationship is a remarkably rewarding and very special bond. However, early in my career, I recognized that I could amplify my impact on women and their families even further through mentorship, leadership, and public awareness. These activities have taken me along many roads but mentoring and sponsoring trainees who are now amongst our most respected leaders in gynecologic oncology is perhaps my greatest legacy and their success is my pride and joy. As editor-in-chief of the journal Gynecologic Oncology, I've worked to raise the bar of clinical science in order to disseminate new knowledge and encourage discovery and excellence. I've strived to never settle for just good enough as we work together to improve outcomes for all women with gynecologic malignancies. And with gynecologic cancers. Like all of you, I look forward to the day when our achievements in cancer care are not only measured by the scientific advances we realize, but also by our ability to provide greater access to better care for all women, no matter where they live. Thank you again for this recognition. Ciao. Dr. Coleman, members of council, and general members of IGCS. Congratulations, Dr. Carlin, on such a very well-deserved recognition of your myriad contributions to the care of women with gynecological cancer. You're an absolute icon. What an honor it is for me also to receive this award. It is a long time since I started this journey in Scotland as a naive medical student, and as you can imagine, I could never have envisaged being here today. I'm a little anxious, however, about the term lifetime, which seems pretty final because there's still lots to do. Top of the list is to have our global nursing curriculum completed under the leadership of Van Mellen from Australia and Noriko Fujiwara from Japan, to develop a series of webinars on the management of cervix cancer by partnering IGCS with the Asian Pacific Economic Cooperation Team, and to explore the possibility of providing radiation services to the women of the South Pacific as part of the WHO NIH plan. Members of IGCS, COVID has been harrowing for us all, but I'm optimistic that in a few years, the worst will be behind us. What a great opportunity then to perhaps get the world's major societies to meet together in a World Congress of Gynecologic Oncology. What a celebration that would be. Finally, thank you to the executive and council of IGCS. Thank you to Mary Iken, CEO, for your support over the last seven years. Thank you to my colleagues in Australia and internationally. Thank you to my family and friends, and particularly to my wife, Susan. And above all, to my patients and their families for trusting me and sharing such a stressful time in our lives. I thank you from the bottom of my heart. It has been such a privilege. Thank you again to all members of the International Gynecological Cancer Society for this hour. I was very honored to receive this hour and I am very emotionated for this hour. Thank you again to this society. This society is very important for many reasons, for educational point of view, for research, for the friendship that this society gives to all our members. My personal medical history begins in Rome, University of La Savienza. I was graduated there, then I was for many years in Catholic University. During these years, I spent two years in National Cancer Institute of Milan, this is a very important step, a major important step in my educational history. I was in the operating room with Francesco Di Re and many very kind colleagues. It is clear that this hour is not only mine, but it's of my teachers, my co-workers, and all the members that have collaborated in this year. My personal gratitude goes to, first, Erich Burgert for this work and for having illustrated the importance of paramedia in cervical cancer. It was important for me and this method I applicated to all the parts of surgery. I want to thank also Paul Knapsen for the clients that he gives me in the plastic surgery, in gynecological surgery. And it was very important, Gian Bamassi and Emilio Imperato for stressing me the importance of vaginal surgery. I have to thank my historical co-workers, in particular, Roberto Angioli, Francesco Manischi, Stefano Gregi, Rosanna Fontanelli, and Francesco Blotti. I spent my last 20 years with my very strict co-workers in this time, which was Giorgia Berniola, Violante Vittonato, and Innocenza Pallaglia. And with this team, I spent a lot of time in the operating room, in the research area. We try in the last 20 years to improve impact of surgery, to tailor the right operation to the patients, and to reduce intraoperative and postoperative complication and reduce morbidity for the patients. To improve quality of life. The operating room represents for me a lot of time where I work, and I fall in love of this place. And this love isn't changed, absolutely. Principal reason is that at the end of operation, the sensation to do something for the patients is priceless, is fantastic. The same sensation have my strict co-workers, especially Giorgia and Violante. And I was very happy to have these co-workers. Finally, I want to thank, sure, my family, especially my wife, Manuela, and all the nurses, and all the patients. Thank you very much again for this award, and good Congress to all of us. It is with great honor and humility that I accept the 2021 Global Humanitarian Award. I know that I follow in the footsteps of many amazing colleagues. It's now been over 20 years since I've started my work in Vietnam, starting at the same hospital where my father was the medical director prior to our leaving the country in 1975 towards the end of the war. My father would have been very proud to know that his children continue to work in the same city, the same hospital, tending to the same people for whom he gave his youth. I want to especially thank my colleagues at the Da Nang IGCS Fellowship Site, especially Doctors Linda Van Lay and Joseph Eng, who have worked so hard to make our fellowship a success. I thank also my friend, Dr. Nguyen Truong, for accepting us into his hospital and for helping us train the fellows. I accept this honor on your behalf. My family made this happen. My wife, Mimi, is now an integral part of our work in Vietnam and has a service project of her own. I thank my wife and my daughter for selflessly give up weeks of summer vacation over the decades to travel to Vietnam and helping me and the team. Finally, I thank the leaders of IGCS who had the foresight and the vision to make the training of physicians in low and middle income countries a priority. It takes courage to stand up for those who are unable to voice their needs. I thank the leaders of our society. I dedicate this award to our fellows. Your work through the years will magnify my small contribution thousandfold. And I thank you for your dedication to our patients. I'm very honored and humbled to receive this award and to join the other recipients today, who I very much admire and respect. Congratulations to all. Education has always been my passion. It runs in my family of many school teachers. Education is a fundamental part of the triad of our mission as GYN oncologists, which is the best patient care, the best education and the best research. Our patients deserve the best. I want to thank my prior teachers and mentors and thank IGCS and those who nominated me and supported my nomination. Many thanks to all my IGCS members, colleagues, and friends and very special thanks to my team at MSKCC who have supported me for more than 20 years. I wish I could be with you in Rome today. I know you're having a wonderful meeting. I wish you all the best and I hope to see everybody soon. Thank you very much. Good day, Dr. Coleman, friends and colleagues. First of all, I have to apologize that I cannot attend the conference physically and I wish you all a foot flow and enjoyable conference, whether you're in Rome or online. I'm honored to receive the 2021 Excellence in Teaching Award. All through my career, I have benefited a lot from my mentors in Hong Kong as well as abroad. Too many people I wish to name. They not only teach me how to become a doctor, administrator, and researcher, and equally important is how to share my knowledge and skills to each others. I have to say that we are learning all the time, not only from our senior, but peers and juniors. If anything that I wish that we should do is to keep an open mind. And take all opportunities to learn from each others. IGCS provides a good platform for us to learn and teach. Just by joining the conference, we know what is the latest development in the field. For those who can attend physically, they allow us the chance to meet others for more in-depth communication. Even if we cannot meet each other, we know that we can learn from each other. We know who to write to and contact. For the dedicated workshops, we send experts to places where it's difficult to travel abroad. For those who can travel, the IGCS young fellows allows the fellows to go abroad and learn. The international fellowship is another milestones that IGCS help places where they don't have a standard training program. And this young fellow, when we turn home, they can set up the formal training and standard that suit their own places. Finally, I have to salute all those who have contributed to teaching and learning in different ways. And the owner of this award should go to them all. Let us keep the torch on and share our knowledge and skill wherever and wherever we go. Thank you. I would like to thank IGCS and its leadership for presenting me with this award. To be considered for the Excellence in Teaching Award is a huge honor and privilege. So thank you, IGCS. I congratulate Rob Coleman, not only for being the youngest and best looking grandpa I know, but also for pulling off an IGCS meeting during extraordinary times during extraordinary times when medical societies like IGCS are trying to keep and hold it all together. As I speak now, large parts of the world are in strife. From the bottom of my heart, I congratulate the other award winners and amongst them are some personal friends. And to you guys, I'm saying, I really miss you. And I'm desperate to catch up for a real chat over BO2. I hope we can do that again in New York next year. I would like to take the opportunity to express my gratitude to a few amazing people whose support is possibly the reason why I speak here. I would like to thank my surgeon teachers who hung in there with me, looked after me, and who were not afraid to let me grow. I mentioned Paul Sevelda from Austria, Alex Crandon from Brisbane in Australia, and Tony McCartney and Ian Hammond from Perth, also in Australia. I thank my colleagues at work in Brisbane here who sometimes lend a hand when I need help to juggle things. There is one person who continues to inspire me and she leads the IGCS advocacy program. Thank you, Dicey Scroggins, for keeping us fired up. And my thoughts and the thoughts of my family are with you while you focus on your own health. And last but not least, I want to thank you all for being part of the IGCS community because with your continued support, gynecological cancer will remain a trending topic. And I'm really proud of the culture that we have and how we talk to each other on Twitter and other medium. Bless you and stay safe. Catch you next year. It's my honor and privilege to accept this award from IGCS. And I'd like to thank Professor Michael Quinn for introducing me to this platform and Dr. Ted Trimble for introducing me to CCRN and GCIG and the members from the Education Committee, IGCS, Mary Iken, Susan Ralph, and many of my colleagues in India, Nepal, and in the UK for contributing towards this process. As you know, 70% of women's cancers are from low middle income countries. There is a huge health gap or inequality in terms of providing access to good quality surgery for ovarian cancer, genetic testing, access to affordable options of therapies like inhibitors. And of course, we are far away from the WHO elimination goal for cervical cancer. So I hope this award provides an inspiration and recognition to work towards bridging this gap through education, training, and research, both in terms of taking part in clinical trials and local representation and translational medicine through creation of more platforms like the Kolkata Gynae Oncology Trials Translational Research Group. And finally, a lot of people are still working towards this goal behind the scenes and without any recognition or acknowledgement. So I'd like to receive this award on behalf of all of them, and especially women in medicine and science who are still struggling to find their feet and being acknowledged for their contribution and commitment and being recognized or accepted as being worth of being called a competent surgeon or a scientist. So thank you, IGCS, once again for this honor. Thank you. First of all, I'd like to thank IGCS for granting me this immense honor. Being a teacher and teaching others is one of the best gifts that life has given me. Being able to contribute in some way to gynecological oncology education in my region, more than a duty, has been a great privilege. Thank you, IGCS, for all the tools you provide to its more than 3,000 members around the world to become better doctors for your patients. I gratefully receive this award on behalf of Latin America, the region that I proudly represent, and I reiterate my willingness to continue working together with countless colleagues from all across the continent to improve the quality of care that we provide to our gynecologic cancer patients. Finally, at last, but not least, I want to congratulate the other awarded, who certainly deserve such public recognitions because their dedication to working in favor of gynecologic oncology cancer patients. I feel myself very privileged to be part of IGCS community. Thank you very much. It's an honor and a privilege to be accepting the IGCS Distinguished Advocacy Award. I'm always amazed by the shift that happens when you connect and empower people to be the change they want to see. Progress against ovarian cancer has taken a group effort. Patients, clinicians, corporate partners, and most importantly, the voices of the women we work with and for are powerful and profound, and they have guided our every move. If you listen and engage, you will always see the way forward. And if you surround yourself with the right partners, everything is possible. As I look forward, this award gives assurance that our work will stand the test of time to have a lasting impact. I share this honor with my team at Ovarian Cancer Canada, 24 years ago, there was no community for women with this disease in Canada. We put tools and resources in place and women and their families came to the table. This award is for those women. They have been my inspiration every day. Regardless of their health, they found hope and purpose being part of a movement so that others would not have to go through what they did. I also must thank my global colleagues for their collaboration. Despite having so much to do in their own countries, they saw the importance of making good on what we knew was possible to benefit women around the world. To all of you, I say thank you and know that transformational change is possible, not overnight, but with perseverance and determination, you can get there. Together, we've demonstrated that. The work we've done for women with ovarian cancer has been such a positive movement. Thank you for this honor. Good afternoon, ladies and gentlemen. I am extremely honored to receive the IGCS Distinguished Advocacy Award this year. And really, so grateful for the IGCS executives for their recognition of my work, of my life, of my efforts. Really, thank you so much to everybody. Well, my story has actually started many, many years ago when I was a resident in Guyana Oncology. I have witnessed the fear and anxiety in the eyes of the cancer patient upon diagnosis. However, after successful surgeries and treatments, I realized that they are changing into very hopeful and living lives. That was my unique motivation, to be the healing hand for them, to be able to touch to their hearts, to be able to improve their well-being. Actually, one patient each time becoming more happy was my real gift. And within years, dozens and dozens of patients were my real motivation. And today, here I am, standing in front of you for such an honorable award. Actually, for me, global female health is in the center of the life. And actually, it's not only me, but all gynecologists in the world deserves actually such an award for the local and regional work on the females. However, I should express some special thanks. First of all, such an award really would not be possible without the inspiration I have received from my patients and from engaged members, from whom I always inspire my energy to do better and better in my advocacy adventures. Thank you so much to ESGO Council and engaged committees for their endless support in my career. On the other hand, some special thanks should go one-to-one. I should thank to Christina Fotopula and Dimitri Haidopoulos, who have nominated me for this award. I should also give my special thanks to Ika Tooth and Esra Aykmez, who have supported all my dreams. Dr. Bekir Keskinkulic, who opened the doors in my life. My team in Turkish Ministry of Health, Cancer Control Department, Hacettepe University Deans and Rectors, my superiors and my colleagues in Turkish Society of Gyne-Oncology and my mentor, Ali Ayhan, for sure. Last but not least, of course, with special coming from my heart, special thanks goes to my wife, my kids, and my family for their endless support in my career. Dear friends, today in front of you, I promise to be committed to work more in the next coming years, to make more to promote the well-being of the patients. But let's do this altogether, hand-in-hand. Let's create a better world against gynecological cancer, hand-in-hand with our patients. Let's use a special motto, working harder to cure our patients is our passion. Thank you so much to everybody here, to all IGCS and all cancer patients around the world. Thank you. Dear ladies and gentlemen, first of all, thank you IGCS for Distinguished Advocacy Award. Many congratulations to the winners of IGCS Award 2021, and also to other award applicants who are doing great work in different parts of the world, but could not make it this year. My best wishes are with them. I'm a trained radiation oncologist with an additional training in cancer control and prevention from NCI USA. I'm currently working as a teaching faculty in a medical college in the government of India. I'm working on cancer prevention and advocacy through Pink Chain Campaign, an Indian society of clinical oncology since 2010, and it has become part of my life now. This award means a lot to me and belong to every individual I work with, irrespective of the hierarchy. Every institutions I had been associated with and the most important, my cancer patient, who made me more positive, kind, and courageous. Thank you so much for making me more human and humble. So this is for my cancer patient. Today, I am missing my pillar of strength and mentor since childhood, my dad, whom I lost last year to cancer. Being a cancer specialist and son of a cancer patient, I'm committed to strengthen the voice of voiceless cancer patient through our cancer awareness campaigns and advocacy programs. I owe my success to my wife, Dr. Shubham Roy, developmental pediatrician, who supported me throughout this journey for a decade now. Thank you IGCS again for this recognition. I'm sure that this opportunity will strengthen us to add more life to each and every day a cancer patient lives. I'm committed to work with IGCS across boundaries to minimize disparities and inequalities in access to cancer care and outcome. Thank you again. Wow. It's so awesome to have the opportunity to listen to each of these awardees. It's a great privilege to be able to, through the IGCS to acknowledge globally people who have contributed so much. Congratulations once again to all the recipients. I can just tell their passion of mentorship, the willingness and wanting to pay it forward and the complete focus on the patient is palpable, just inspiring. Obviously their recognition is well-deserved and they motivate us all to know what's capable and inspire us all to undertake those ambitious projects and strive to continue to do better. So with that, I'm gonna conclude the award ceremony and we'll now move on to the seminal abstract session. And in doing so, I'd like to welcome IGCS 2021 Scientific Committee co-chair Dr. Anna Wachman, along with our past president, Dr. Roberto Angiolini, who will moderate the next portion of the session. Thank you, Rob. Thank you, Dr. Coleman for sure. My congratulations to all of the awardees. So amazing and touching speech. I've enjoyed a lot. So I'll transition us into the scientific session with four seminal abstracts up next. I would like to say that after the presentation, we will open up for a question and answer segment. So please, everyone view, please submit your question as the presenters are speaking and we will address as many as we can at the end of the presentation. Without further delay, it's my great pleasure and honor to introduce our first presenter, the very well-known David O'Malley. Please, David, the floor is yours. Thank you, Anna. Boy, I'm so humbled after such amazing individuals and recognition. Rob, once again, I owe you, that's a tough act to follow. Thanks for taking care of me, my friend. But, you know, no, I really, truly, I mean, I am sitting here, tears in my eyes, just the passion and it's a great reminder to us all of what can be accomplished as we work together. So on that note, it is my honor to be, to present on behalf of my co-authors. I'd like to take this opportunity to thank originally ASCO and now IGCS, the Program Committee and the members of the Scientific Review Committee for the opportunity to present this important final analysis of rituximab-sorabtansine, a fully receptor alpha-targeting antibody drug conjugate or ADC in combination with bevacivumab, which I'll call BEV in patients with platinum agnostic cancer. These are my disclosures. Interestingly, Parpenhinders are moving to earlier lines of therapy as maintenance and in larger defined populations. The use of maintenance therapies are extending the platinum-free interval, thus leading to additional lines of platinum-based therapy, leading to a higher occurrence of platinum hypersensitivity. More patients are living long with recurrent ovarian cancer on a need of treatment alternatives, especially after platinum therapies are no longer an option. Rituximab or MIRB delivers the potent tubulin target of a tansinoid DM4 directly to the tumor in patients expressing fully receptor alpha and has demonstrated significant activity in platinum-resistant ovarian cancer. This includes both as a monotherapy and in combination with BEV with an overall response rate up to 56%. Additionally, we are all well aware of the improved progression-free survival and response rates when BEV is added to cytotoxic therapies. This trial combined MIRB and BEV in a broader segment of recurrent ovarian cancer patients regardless of platinum status. The primary, I apologize, the primary objective of our trial is to assess the response-based antitumor activity of the combination of MIRB plus BEV in patients from whom a non-platinum-based doublet would be appropriate. Up to three prior therapies were allowed. Using immunohistochemistry-based scoring, the MEV-2 was evaluated based on medium, at least 50%, but less than 75% of cells, and high, at least 75% of cells, with at least two plus standard intensity for fully receptor alpha expression. MIRB was given at six milligrams per kilogram, adjusted ideal body weight, along with standard BEV dosing every three weeks. Here are the demographics. Two-thirds of patients enrolled had received two or more prior therapy. 13 of 60 patients had high folate receptor alpha expression. 40% had prior BEV use, and 35% had prior PARP use. Approximately one half were platinum-resistant. Of those with platinum-sensitive disease, of those with platinum-sensitive disease, the majority had a platinum-free interval of less than six months. Overall response rates are shown here. Of note is the 64% confirmed overall response rate in patients with tumors with having a high folate receptor alpha expression. The combination of MIRB plus BEV and high folate receptor alpha patients was highly active in both platinum-resistant and platinum-sensitive disease, with confirmed response rates of 59 and 69% respectively. These responses were durable with a median duration of response of nearly a year in patients with high folate receptor alpha expression. In those patients with a high folate receptor alpha expression and platinum resistance, the median duration response was 9.4 months. And those with recurrent platinum-sensitive disease, the median duration response was almost 13 months at 12.7. Looking closer at those patients with high folate receptor alpha expression in the waterfall plot on the left, 97% of patients demonstrated a reduction in tumor burden in patients with both platinum-resistant and platinum-sensitive disease. 97% had tumor reduction. These deep responses are rapid and durable as can be seen in the spider plot on the right in both platinum-sensitive and platinum-resistant patients. Many of these durable responses continue beyond six and 12 months, with some patients' responses last more than two years. I recently saw one of my patients who's coming up on almost three years of therapy. Turning to progression-free survival, the Kaplan-Meier curves, like the data for overall response rate and duration response, demonstrated that patients with high folate receptor alpha benefit the most from the combination of MIRV and BEV, with a median progression-free survival of 10.6 months overall. In addition, in the high folate receptor alpha patients, the six-month progression-free survival was 80%, and the 12-month progression-free survival was 42%. Let's think about that for a second. Six-month progression-free survival rate of 80% and 12 months at 42%. The median progression-free survival in these high folate receptor alpha patients remains nearly 10 months in those with platinum-resistant disease, and over 13 months in those places classified as platinum-sensitive. Treatment-related adverse events were mostly low-grade and manageable. Grade three or more events were infrequent, and as expected in this patient population. Grade three or more adverse events with a frequency of more than 10% included 17% of patients with hypertension and 13% with neutropenia. 18 patients or 30% discontinued BEV and or MIRV did treatment-related AEs. These discontinuations occur with a median of 13 cycles of treatment. So again, 30% discontinued with a median of at 13 cycles of treatment. So more chronic in nature. And when adjusted for exposure, adverse events were similar for MIRV plus BEV compared with MIRV alone. The exceptions include diarrhea, fatigue, hypertension, dysphonia, and weight decrease. In conclusion, in conclusion, the combination of MIRV plus BEV was highly active in a broad population of recurrent ovarian cancer patients with high folate receptor alpha expression. These patients represent a growing population in need of more effective, well-tolerated, and non-platinum treatment option. A 64% overall response rate, 11.8 month median duration response, and 10.6 month median progression-free survival with a combination of MIRV and BEV regardless of platinum status is very exciting and a compelling finding. In those patients with recurrent platinum-sensitive disease, most of them would have occurred within 12 months of their last regimen, 69% overall response rate, 12.7 median duration response, and 13.3 month median progression-free survival is very compelling in light of expectations for platinum-based doublet therapy in less heavily treated populations. Patients with platinum-resistant, over half of whom had three prior lines of therapy, also demonstrated a remarkable overall response rate of 59%, duration response 9.4, and progression-free survival 9.7, well exceeding expectations for chemotherapy, BEV chemotherapy combinations in platinum-resistant patients. These data add to the previously reported and support MIRV as a combination partner of choice for BEV in high folate receptor alpha ovarian cancer patients following the use of platinum-based treatment. Further development of MIRV in combination of BEV is warranted. We are truly indebted to the patients who participated in this trial. And I'd like to thank the investigators who also contributed. But really, without the patients, we wouldn't be able to perform such exciting research, really delivering tomorrow's therapies today. Thank you. Thank you, David, for your great presentation. After an amazing award session, we are having a very impressive scientific session. We will have the Q&A after the full presentation. So next up, we have Vicky Maker. Vicky, please share your screen. You can go ahead with the presentation. Thanks. Hello, everyone. It is my immense privilege to join you all today. And before I begin, I just wanted to express my heartiest congratulations to all the award recipients today. Truly inspiring to join you today. And I'm really privileged to be here. Congratulations, Dr. O'Malley, on your incredibly impressive data in ovarian cancer. And now we will shift gears to the world of endometrial cancer. So on behalf of my esteemed co-authors, I would like to thank the IGCS Selection Committee for affording me the opportunity to present as a seminal presentation our results of Study 309, Keynote 775, a multicenter, open-label, randomized Phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer. Here are my disclosures. As you're aware, this material was previously presented at the Society of Gynecologic Oncology 2021 meeting, and the health-related quality of life data was also presented at ASCO 2021. So as we know, at this time, there continues to be a tremendous unmet need for the development of effective therapies to treat advanced recurrent endometrial cancer, and no global standard second-line treatment as yet has been identified. Checkpoint inhibitors, of course, have previously shown benefit in MSI-high and mismatched repair-deficient tumors. And in Keynote 146, a Phase II study in previously treated advanced recurrent endometrial carcinoma, lenvatinib plus pembrolizumab showed compelling efficacy with manageable safety profiles. In this Phase III study, we compared the efficacy and safety of lenvatinib, or len plus pembrolizumab, or PEMBRO, versus treatment of physician's choice, or TPC, following platinum-based therapy in advanced recurrent endometrial carcinomas. Key eligibility criteria included advanced metastatic or recurrent endometrial cancer with measurable disease by RESIST 1.1 per blinded independent central review. Patients had to have one, but were allowed two prior lines of platinum-based therapy if one was administered in the neoadjuvant or adjuvant setting. There was no restriction on prior hormonal therapy. Patients were stratified by MMR status, and within the MMR-proficient cohort were further stratified by region, ECOG status, and prior history of pelvic radiation. Eligible patients were randomized one-to-one to LEN 20 milligrams orally once daily, plus PEMBRO 200 milligrams IV Q3 weeks, versus TPC of doxorubicin 60 milligrams per meter squared IV Q3 weeks, or Paclitaxel 80 milligrams per meter squared weekly three weeks on, one week off. PEMBRO could be administered for a maximum of 35 doses with LEN continuing beyond that point if a patient was clinically benefiting, and the maximum cumulative dose of doxorubicin allowed on study was 500 milligrams per meter squared. Primary endpoints were progression-free survival by BIKR and overall survival. Secondary endpoints included objective response rate and quality-of-life analyses, and key exploratory endpoint was duration of response. A graphical approach from multiplicity to control for type 1 error was utilized to test progression-free survival, first in PMMR and then all-comers cohorts, followed by overall survival and objective response rate for PMMR and then all-comers populations. Importantly, the all-comers population included the DMMR patients. Efficacy analyses were conducted in randomized patients. Safety analyses were conducted in all patients who received treatment. The first interim analysis, which detailed the final PFS and interim OS was triggered by approximately 368 OS events in the PMMR patients with greater than or equal to six months of follow-up. Data cutoff for IA1 occurred approximately 8.5 months after the last patient was randomized. PFS and OS were evaluated by stratified log-rank test. Hazard ratios were evaluated by Cox proportion hazard model. Power calculations, importantly, were based on the PMMR population. In this study, 827 patients were randomized between the two arms. The arms were balanced with regards to age, prior RT, ECOG status, and race distribution. 84% of patients in both arms were PMMR. Full histologic spectrum was balanced between arms. Endometrioid adenocarcinomas were the most common histology, representing approximately 60% of cases in both arms, and the distribution of low-grade and high-grade endometrioid adenocarcinomas were comparable between arms. Serious histology at just over 25% was the most common non-endometrioid subtype, followed by clear cell and mixed histologic subtypes, and their proportions are relatively balanced between treatment arms. Seventy-nine percent in the LEN PEMBRO and 76% of patients in the TPC arm had one prior platinum-based therapy, and 55% in the LEN PEMBRO versus 60% of patients in the TPC arm received neoadjuvant and or adjuvant platinum-based chemotherapy. In this study, statistically significant improvements in both progression-free survival and overall survival were seen with LEN PEMBRO compared to TPC in both the PMMR and all comers populations. Here we see PFS for the PMMR and all comers cohorts. The median PFS for the PMMR cohort was 6.6 versus 3.8 months for LEN PEMBRO versus TPC, respectively, with a hazard ratio of 0.6. In all comers, the median PFS was 7.2 versus 3.8 months for LEN PEMBRO versus TPC with a hazard ratio of 0.56, and the curves separate early and at approximately the first radiologic assessment. PFS analysis in all assessed subgroups, including MMR status, histology, and prior lines of therapy showed a significant advantage for LEN PEMBRO. Despite informal crossover, when LEN PEMBRO became approved in many countries based on Keynote 146 results in September of 2019, with a median follow-up of 11.4 months, the overall survival for the PMMR cohort was 17.4 versus 12 months for LEN PEMBRO versus TPC with a hazard ratio of 0.68. OS for all comers was 18.3 versus 11.4 months for LEN PEMBRO versus TPC with a hazard ratio of 0.62. Again, the OS curves separate early and at approximately three months. And as we saw for PFS, OS analysis in all assessed subgroups, including MMR status, histology, and prior lines of therapy also showed an advantage, significant advantage for LEN PEMBRO. In both the PMMR and all comers cohorts, the objective response rate was doubled with LEN PEMBRO compared to TPC. In the PMMR cohort, the objective response rate was 30 versus 15%, and an all comers cohort was 32 versus 15% for LEN PEMBRO versus TPC. CR and PR rates were also approximately double for LEN PEMBRO versus TPC. The median duration of response in the PMMR cohort was 9.2 versus 5.7 months for LEN PEMBRO versus TPC, and in all comers, the median duration of response was 14.4 versus 5.7 months for LEN PEMBRO versus TPC. Median time to response in the PMMR cohort was 2.1 versus 3.5 months for LEN PEMBRO versus TPC, and in all comers, the median time to response was 2.1 months for both treatment arms. The median duration of treatment in all comers was more than double for LEN PEMBRO at 231 days versus 105 days for TPC, and this is important to keep in mind as we talk about treatment emergent adverse events. Grade 3 or greater treatment emergent adverse events occurred in 89% versus 73% of patients on LEN PEMBRO versus TPC. Study drug interruption occurred in 69% of patients on LEN PEMBRO versus 27% of patients on TPC. LEN was interrupted in 59%, PEMBRO in 50, and both were interrupted in 31% of patients. Study drug discontinuation occurred in 33% of patients on LEN PEMBRO versus 8% of patients on TPC. LEN was interrupted in 50%, PEMBRO in 50, and both were interrupted in 31% of patients. The most common NE grade TEAEs for LEN PEMBRO were hypertension, hypothyroidism, which was predominantly grade 1 or grade 2, diarrhea, nausea, and decreased appetite, whereas with TPC, anemia, nausea, neutropenia were most common. Grade 3 or greater events occurred in 99% of patients on LEN PEMBRO versus 8% of patients on TPC, and this is important to keep in mind as we talk about treatment emergent adverse events. Grade 3 or greater events occurred in 89% of patients on LEN PEMBRO, and the most common were hypertension in 38% followed by weight decrease, decreased appetite, and diarrhea, each occurring in 10% of patients or less. Grade 3 or greater events occurred in 73% of patients on TPC, and the most common were cytopenias. Regardless of causality, grade 5 events occurred in 5.7% of patients on LEN PEMBRO, 21% of which versus 4.9% of patients on TPC, 30% of which were due to infections. Assessment of health-related quality of life was a key secondary endpoint of this study, and here we show a summary of health-related quality of life data at baseline and from baseline to week 12. Instruments utilized for this endpoint included the EORTC QLQ-C30, which assessed global health status, quality of life, and physical functioning, the EORTC QLQ-EN20, which assessed urological symptoms, and the ED, sorry, EQ5D5L visual analog scale, all scales measured from 0 to 100, and in this table, with the exception of QLQ-EN24, higher scores represent better functioning and quality of life. The analysis dataset included treated patients who had one or more health-related quality of life assessment available. Changes in quality of life were analyzed from baseline to the last time point at which overall completion was 60% or greater, and overall compliance was greater than or equal to 80% using constrained longitudinal data analysis. And baseline global health status and quality of life scores were similar between the lenvatinib plus pembrolizumab group and the TPC group, and no substantial differences in quality of life scores were observed from baseline to week 12 between the two treatment groups. Changes in quality of life scores from baseline over time are shown here. Overall, scores were generally maintained over time from baseline and were similar between the two groups during the evaluation period, and no significant differences were observed in quality of life scores between treatment groups. In conclusion, lenvatinib plus pembrolizumab showed statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and objective response rate versus treatment of physician's choice in PMMR and all comer endometrial cancers following platinum-based chemotherapy. Benefits with regards to PFS and OS were observed across all analyzed subgroups, including histology and number of prior therapies. No substantial differences in quality of life scores were observed over time between the two treatment groups, and lenvatinib plus pembrolizumab had a manageable safety profile that is generally consistent with the established safety profiles of the individual monotherapies. Based on this compelling data, in July of this year, the FDA granted full approval to combination lenvatinib and pembrolizumab for the treatment of advanced endometrial carcinoma that is not MSI high or mismatch repair deficient following disease progression on prior systemic therapy in any setting, and for those who are not candidates for curative therapy. My co-authors and I would like to express our deepest, deepest gratitude to all patients and their families, as well as to all the investigative teams who participated in this study. I thank you for your kind attention. Thank you so much, Dr. Marker, for this excellent work and this excellent presentation. In fact, this will represent a really turning point in endometrial cancer treatment landscape. Thank you for all your work for endometrial cancer patients. So now is the time to present Professor, I'm sorry, Professor Rebecca Christallet. So please, Rebecca, the floor is yours. We are excited to hear your presentation. Many thanks, Anna. So good afternoon, everyone. I'd like to thank the IGCS organizing committee very much, especially following such a glittering award ceremony, the opportunity to present on behalf of the global investigator team, the efficacy and safety results from ARIEL4. ARIEL4 is a randomized phase three trial of Rucaparib versus chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA mutation. This is an encore presentation following sharing of this data at SGO and the ESMO Gynecological Cancer Conference earlier this year. Apologies, these are my disclosures. The PARC inhibitor Rucaparib is approved as monotherapy, that is, instead of chemotherapy, for patients with BRCA mutated relapsed ovarian cancer who have received at least two lines of platinum-based chemotherapy. This approval was granted following submission of pooled data from two early phase trials, Study 10 and ARIEL2. ARIEL4 is a confirmatory phase three trial evaluating the efficacy and safety of Rucaparib compared to standard of care chemotherapy in patients with BRCA mutated relapsed ovarian cancer. The study was designed and approved in consultation with both the FDA and the EMA. Patients with relapsed ovarian fallopian tube or primary peritoneal cancer were enrolled to ARIEL4 and had to have received at least two prior lines of chemotherapy, including at least one prior platinum-based regimen. Subjects were also required to have a tumor with a deleterious BRCA mutation, either somatic or germline, and could not have received prior PARP inhibitor or single agent paclitaxel. The study population included platinum-resistant patients defined as relapsed between one and six months after platinum, partially platinum-sensitive patients defined as relapsing six to 12 months after platinum, and fully platinum-sensitive patients defined as relapsing over 12 months after their last platinum. Platinum status was a stratification factor for randomization in a two-to-one manner to either 600 milligrams twice a day of Rucaparib or chemotherapy. Weekly paclitaxel was given to patients who were platinum-resistant or partially platinum sensitive, and platinum-based chemotherapy, doublet or single agent, according to investigator choice, if fully platinum-sensitive. This schema illustrates patient flow within Arial4 with two-to-one randomization to Rucaparib versus chemotherapy. Overall, 349 patients were enrolled. 233 patients were randomized to receive Rucaparib, and 116 to standard of care platinum or non-platinum-based chemotherapy, depending on the patient's platinum sensitivity. On progression, 64% of patients on the chemotherapy arm crossed over to receive Rucaparib, which was allowed within the study. For analysis, the intention to treat population included all randomized patients. The efficacy population excluded patients found to have a BRCA reversion mutation at study entry, of which there were 23, 13 in the Rucaparib arm and 10 in the chemotherapy arm. One patient who did not have a deleterious BRCA mutation was also excluded from the efficacy population. The total efficacy population, therefore, was 220 in the Rucaparib arm and 105 in the chemotherapy arm. At the time of data cutoff, 44 patients continued to receive Rucaparib, and five continued to receive chemotherapy. The statistical analysis plan for efficacy endpoints is shown here. The plan comprised a pre-specified hierarchical testing used for multiplicity between the populations. The primary endpoint was investigator-assessed, progression-free survival in the efficacy population. Overall survival is a standalone efficacy endpoint outside the hierarchical analysis. The baseline patient characteristics of the intention to treat population were well-balanced. Just under 60% of patients were recruited from Central and Eastern Europe, with North and South Europe and America recruiting just over 40%. 95% of patients had epithelial ovarian cancer, 90% had serous and 7% endometrioid histology. 84% of patients had a germline BRCA mutation, the remainder being somatic. 58% of patients had received two prior lines of BRCA, and the remaining 50% had received three or more lines of chemotherapy, and 42% had received three or more. 66% of patients had received two prior platinum-based therapies. 22% of the study population had a non-platinum regimen immediately before trial participation. The platinum sensitivity distribution was 51.3% with platinum-resistant disease, 27.5% with partially platinum-sensitive disease, and 21.2% who were fully platinum-sensitive. 95% of patients had measurable disease at baseline. Presented here are the results of the primary endpoint of investigator-assessed progression-free survival in the efficacy population. As you can see, RUCAPRIB showed a statistically significant improvement in median progression-free survival compared to chemotherapy, with a hazard ratio of 0.64. The median progression-free survival observed in the RUCAPRIB arm was 7.4 months, and in the chemotherapy arm 5.7 months, an improvement of 1.7 months. The investigator-assessed progression-free survival in the attention-to-treat population is shown here. This was also statistically significant, and showed the same absolute improvement in median progression-free survival as the efficacy population for RUCAPRIB compared to chemotherapy, of 1.7 months, this time with a hazard ratio of 0.67. As mentioned before, 23 patients were found to have a BRCA mutation, were found to have a BRCA reversion mutation at the point of study entry, 13 in the RUCAPRIB arm and 10 in the chemotherapy arm. Although the number of patients identified with a BRCA reversion mutation using analysis of circulating cells is very small, these results do suggest that the presence of a BRCA reversion mutation may predict for reduced benefit from RUCAPRIB treatment. This is demonstrated by the observed 2.9-month median progression-free survival with RUCAPRIB in this population, compared to 5.5 months in those receiving chemotherapy. The secondary endpoint of overall response rate was 40.3% for RUCAPRIB and 32.3% for the chemotherapy arm, although this difference did not reach statistical significance. Therefore, the hierarchical statistical analysis was broken at this point. The duration of response, however, was longer following RUCAPRIB treatment at 9.4 months compared to 7.2 months with chemotherapy and a hazard ratio of 0.59. Data were very similar for the intention to treat population. Change from baseline in global health status using the EORTC QLQC30 tool was a secondary endpoint of this trial. There was no difference identified in global health status compared to baseline in either the RUCAPRIB or chemotherapy arm in either the efficacy or intention to treat populations. Data was available up to day 1 of cycle 7, equivalent to 24 weeks on study. In a pre-specified exploratory analysis of investigator-assessed progression-free survival in the efficacy population of platinum sensitivity subgroups, data initially presented by Professor Amin Oza at ASCO 2021, we see that RUCAPRIB is consistently at least as good and possibly better as chemotherapy across all these subgroups, platinum-resistant, partially platinum-sensitive, and fully platinum-sensitive populations compared to weakly paclitaxel or platinum-based chemotherapy. Treatment emergent adverse events reaching over or equal to 20% in either arm are shown here in the safety population. 232 patients treated with RUCAPRIB and 113 with chemotherapy. Any grade as well as greater than or equal to grade 3 TEAEs are shown within the bars in blue or gold respectively. There are no new emerging toxicities identified in either treatment arm. Although rates of anemia and thrombocytopenia appear slightly higher with RUCAPRIB, the median duration of treatment with RUCAPRIB is actually double that of chemotherapy. 8.2% of patients in the RUCAPRIB arm and 12.4% in the chemotherapy arm discontinued treatment due to treatment emergent adverse events. Myelodysplasia or acute myeloid leukemia was reported in five patients in the RUCAPRIB arm. In conclusion, patients with BRCA-mutated advanced relapsed ovarian cancer who received RUCAPRIB had a significant improvement in progression-free survival over standard-of-care chemotherapy. RUCAPRIB-treated patients had comparable or longer progression-free survival versus chemotherapy, importantly across all platinum status subgroups. The RUCAPRIB safety profile was consistent with that reported in prior studies, and this is the first prospective report as far as we're aware from a randomized study demonstrating that the presence of a BRCA reversion mutation may predict for primary resistance to RUCAPRIB. Overall survival from this study will be presented when death events are mature, and this is expected when at least 70% of death events have been reported. Finally, I would like to acknowledge my co-investigator Professor Amit Oza from the Princess Margaret Cancer Centre in Toronto and the invaluable contribution of all patients that participated in this study and made it possible, as well as the entire team of investigators around the world. Thank you for your attention. Rebecca, ARIA4 is a very important study on ovarian cancer and I really like to thank you for sharing with us this clear in-depth analysis of the study. Now we move to our final presentation. We have Kathleen Moore. Dr. Moore, please can you share your screen? Okay, you can go ahead with your presentation. Great. Well, thank you. It's my great honour to round out this outstanding session today and I greatly appreciate the opportunity to present GOG274, the Outback Trial, on behalf of the international investigators. This is an encore presentation of the presentation by Dr. Linda Milshkin at ASCO just this year. These are my disclosures. So, this audience is no stranger to this data. Cervical cancer is a major global problem. It's the fourth most common cancer of women worldwide with a staggering half million, over half million cases and over a quarter million deaths per year. The vast majority of cases occur in less developed regions of the world where cervical cancer comprises nearly 12% of cancers in women. Local regionally advanced cervical cancer presents disease that renders them not amenable to radical hysterectomy and have greater rates of metastases and poor disease-specific survival than organ combined cervical cancers. Now, we did of course make some inroads here, really two decades ago, with the incorporation of platinum-based chemotherapy into the radiation schema for patients with local regionally advanced disease. And as you can see here, this did result in an improvement in overall survival for women with local regionally advanced cervical cancer, but we still have, unfortunately, treatment failures and these So, let me just remind you about why this study was designed, why the Outback Study was even thought of as a good idea. We had several kind of smaller studies, and you see this meta-analysis outlining them, but really three big large phase three randomized trials treating women with either local regionally advanced disease or high risk disease following radical hysterectomy. All of them had at least one extra dose of chemotherapy after the completion of chemotherapy and radiation. So RTOG 9001 used one additional cycle of cisplatin and 5-fluorouracil following external beam radiation. The Duenas-Gonzalez protocol used two additional cycles of cisplatin and gemcitabine, of course after external beam, and GOG 109, which was of course in high risk, mainly node-positive disease following radhyst, but here used two additional cycles of cisplatin and 5-fluorouracil following external beam radiation. And all of these studies when compared to either their internal comparison, as well as historical controls, appeared to have a signal of superior outcomes as compared to chemo RT alone. And so this study was really felt this finding of maybe this extra chemotherapy or what we've called outback chemotherapy was felt to be promising, but of course needed a confirmatory trial. And so that's why outback was designed. And so here's the study schema. It was a patient, it was a study that enrolled women with local regionally advanced cervical cancer. So they could be 1B1 with positive lymph nodes. There weren't many of those, or as 1B2 through 4A, they had to have good performance status. They could be of any histology and they could not have positive periodic nodes. They could have positive pelvics, but they could not have positive periodics. They're randomized one-to-one to standard concurrent chemo RT with cisplatin or the same followed by a planned four cycles of adjuvant chemotherapy here designated as ACT with carboplatin and paclitaxel. And you see the stratification factors listed below. Now the primary endpoint here is overall survival and the secondary endpoints are as listed in the box on the right. Just to remind you what the study treatments were, and this was designed to be a global study. So it tried to harmonize across many countries, but patients got pretty standard therapy with 40 to 45 gray of external beam in standard fractions plus brachytherapy and then cisplatin 40 milligrams per meter squared weekly versus the same plus four cycles of paclitaxel carboplatin given in AUCO5 and paclitaxel 155 milligrams per meter squared every three weeks for four cycles. Now this study underwent some statistical amendments during its life cycle. The original protocol was written as 780 participants a planned for 80% power with a two-sided alpha for an absolute improvement of 10% in overall survival at five years using historical benchmarks, which were 63% for the control group improved to 73% with three years accrual and a median time to recurrence of 12 months. I apologize for my dog. This was amended during the course of the study in 2016 to 900 participants, still 80% power in a two-sided alpha, but here to improve the overall survival, which had been adjusted from 72% now in the control to 80% to account for a couple of things. One is non-adherence to the adjuvant chemotherapy, and I'll get back to this. So at this point, 16% of women who were assigned adjuvant chemotherapy had not started it, and then really a lower than expected event rate, which is a good thing in the patient population. The primary analysis was still a direct comparison of survival rates at five years, and then you can see the secondary analyses below. Here's the CONSORT diagram for those patients who were randomized. So we went to 926 patients randomized evenly in a one-to-one, as was the plan, and you can see the distribution of patients who started chemoRT, completed chemoRT, and both arms was very similar and a little bit low. And then you can see the number of patients that were included in the survival analyses, and we have five years of follow-up for this clinical trial. Here are the baseline characteristics, starting with demographics, and this is a very standard population for cervical cancer, at least as we've studied it thus far. I'll just call out the fact that even though cervical cancer is a disease that largely impacts women in developing countries and underrepresented minorities, we still unfortunately had a large proportion of patients who were Caucasian, owing to the countries in which this was studied. So we had a large proportion of this was open, so you'd have to question whether or not this represents the globe, and about 50% of patients were smokers. Now looking at the disease characteristics, just calling out the fact that about 50% of our patients who were enrolled had positive lymph nodes, so a relatively high-risk group of patients, and the vast majority, as expected, were squamous cell, about 80%. Now here's the chemoradiation adherence, so this is just talking about chemoRT alone. What you can see is approximately 83% of patients completed all five assigned doses of their cisplatin, which is okay, but only 77% finished the whole course of cisplatin, either four or five cycles, we gave them one off, and radiation. So almost a quarter of patients had some missing treatment, either chemoradiation fractions or both. Now looking specifically at the adjuvant therapy, for those women who were randomized to the adjuvant chemotherapy arm, what happened here? Well, about 27% or exactly 27%, 22% got none, they just decided they didn't want to start, an additional 5% stopped after only one cycle, so about 27% of patients received one or fewer of their assigned cycles of chemotherapy, and this was presented by Dr. Mielchikin at ESMO in 2019 as to the reasons why women did not start, and it was really associated with age, so women over 60 were less likely to start. This group comprised only 15% of our population in non-Caucasian women, and it tripled in those who didn't finish their chemoRT, so lack of adherence to chemoRT predicted lack of adherence to the assigned adjuvant chemotherapy, which kind of makes sense. So the survival analysis is performed in the intention to treat population, even given these limitations, and as we all know, here are the results. So the overall survival, which is our primary endpoint with 60-month median follow-up, shows absolutely no difference with use of adjuvant chemotherapy versus standard chemoRT alone in this population. You can see the FIGER overall survival estimates at 71 and 72%, which is about what we have seen historically. Now even looking at progression-free survival, again, no signal of superiority with addition of additional chemotherapy with a non-significant p-value and five-year progression-free survival percentages that look, again, like our historical controls. Now we can look at the subgroups here, and really overall you don't see any subgroups called out that seem to benefit from the addition of chemotherapy, which was somewhat surprising to me. I thought maybe those node-positive patients or the larger tumors, those with higher risk for distant failures would benefit, and we really did not see any signal of this whatsoever in this analysis. And in fact, really the only call-out is age, and those women who were over 60, which is again only 15% of this population, so it's a very small number, but they seemed to benefit more from just chemoRT alone, not adjuvant therapy. You know, what that means is kind of yet to be determined because it's such a small group, but they certainly didn't benefit from additional therapy. Now if we look at the patterns of disease recurrence, really suffice it to say that there were no differences. Despite 50% of patients having no positive disease, the percentage of patients who never had recurrences was relatively high at 67 and 72%. The local regional alone recurrences were 7 and 10%, and then the remainder were distant plus minus local regional, so really no impact on reducing distant metastases, which would be the expectation with additional chemotherapy demonstrated in this study. Adverse events were what you would expect if you add paclitaxel and carboplatin following chemotherapy, so there was statistically significantly more hematologic toxicity, alopecia, fatigue, all of the things that you would normally expect, but nothing out of range for what you would expect with use of paclitaxel and carboplatin, so the safety signal was very consistent with what we expect with chemotherapy in general, and febrile neutropenia was the same, very low, 2% in both arms. And similarly, if you look at non- hematologic side effects, you did see statistically significantly more things that are associated with paclitaxel and carboplatin amongst women who received paclitaxel and carboplatin, but there was nothing surprising, and really at one year, the only thing that you saw that was different, again not a surprise, is more grade 2 or higher peripheral neuropathy in those patients who received adjuvant chemotherapy at 7% versus only 2% in those who received chemoRT alone. Now we did look at global quality of life using the global health scale items 29 and 30 of the QLQC30, and you did see impaired quality of life during and shortly after adjuvant chemotherapy, but then by month 12 and certainly to 36, it was similar. And so this again is what you would expect if you're using chemotherapy versus someone who's not receiving chemotherapy. Now I mentioned to you that there was about a quarter of women who did not receive their assigned adjuvant chemotherapy, and so there was interest in sort of looking at the patient population who did and seeing if there was an improvement with an overall survival with adjuvant chemotherapy, particularly in this group. And as you can expect, this is a very biased analysis because there are differences in patients who did and did not finish their chemotherapy, but irrespective of that, we still did the sensitivity analysis based on who did or didn't complete their chemoRT just to see if there was an association with those who completed the adjuvant chemotherapy. And there certainly was an effect. There wasn't, as I mentioned, failure to complete chemoRT was the strongest predictor of not starting adjuvant chemotherapy, but there weren't really differences between the subgroups that were greater than expected by chance alone when you applied this analysis to the survival curves. So this is a very biased analysis. I think the bottom line, failure to finish chemoRT predicted not starting adjuvant chemotherapy. Of course, we see some differences in outcomes between those groups, but that analysis is really too biased to even show or make any definitive statements about. So in conclusion, really, I think the take-home point is for those of you that were early adopters of additional chemotherapy following chemoRT in women that you felt were high risk for treatment failure, you should stop because we demonstrated absolutely no improvement in overall survival, which is our primary endpoint or progression-free survival, and concurrent chemoRT continues to be the standard of care until we hear the results of the ongoing TALUS study and the ongoing Merck study with incorporation of immune checkpoint inhibitors into the same population. And further research is ongoing, should focus on immunotherapies and other adjuvant therapies that may be more tolerable and effective, as well as identifying women who are at highest risk for treatment failure so that those women can be preferentially offered additional therapies, and those that are cured with our standards can receive that alone. As always, a great deal of thanks to the women who participated in this study across many countries, to the ANZCOG Coordinating Center and Dr. Milchkin for her exceptional leadership of this study, and to the GOG and the GOG supporting sites who were amazing partners, and I thank you for your attention. Thank you so much, Katie, for this important trial, and thank you for your great presentation. So I will invite all the speakers to join this latest part of the session, question and answer, and I invite all the attending, you know, to make your questions through the chat. So I will start with Rebecca, because we have received a question from the audience. One of our colleagues asked if you will explain to them what do you define BRCA reversion and how would you determine BRCA reversion in the ARIEL4 trial? Thank you. So BRCA reversion mutations were actually identified prospectively from circulating tumor cells, so it's using an analysis platform where you take a blood test and you analyze within the blood test in tumor cells whether, if there were circulating tumor cells or in the blood test, whether there was a reversion mutation present in that blood test. Now the blood test was taken at the point of study entry, but it wasn't analyzed until obviously the end, once we were analyzing the primary endpoint. So the BRCA reversion mutation status, remember these patients have not previously had a PARP inhibitor, was actually assessing a de novo resistance status. It's not a resistance that's acquired due to the PARP inhibitor. So yeah, I think that was, I think that answers the question. I think so, I think so. So we have received another question for Kathy related without that trial. Kathy, one of the questions is how do you determine the positivity of the lymph nodes in the trial, either by histological confirmation or just by imaging? It was by imaging, so it was not histologic confirmation. We discussed this quite a bit at the beginning. Really it was if the investigator felt that it was positive, either the CT had recessed measurable nodes or if the PET CT was calling positive nodes as well, those would be listed as positive nodes. So it was by either. Okay, and I have an additional question for you. When you review the baseline patient characteristic, only 50% of the population had positive lymph nodes and the majority of them just pelvic lymph nodes. No one had a periortal lymph node because it was an exclusion criteria. So my question is, have we enrolled the right high-risk population of cervical cancer to be able to determine a benefit from adjuvant chemotherapy? Yeah, I think we, every time we do one of these studies, we learn. It's kind of like even the adjuvant endometrial, right? We keep figuring out the group that is the highest risk over time. So no, I think that we didn't. We thought we did. Local regionally advanced disease certainly does have still a 25 to 30% treatment failure rate. So it is, I think, still high risk, but who are the patients whose tumors recur? Node positivity, size, or there's some, we're going to hear a presentation later today on perineural invasion. Is it something that we can identify to really hone in on that group of women who really need extra stuff more is more versus those who are cured? There's some who are cured with radiation alone. They don't even need the cisplatin. So we just haven't gotten that granular yet. I do think the Calis study, which is completed, did attempt to enroll a much higher risk population in this one. And so that's probably going to be kind of our next big learning point there. And then Merck has an ongoing study as well. So every time we do this, I feel like we kind of hone in on the population. Do we have it right yet? This one's too low risk. Thank you, Cathy. I have another question for Vicky. Vicky, there's no doubt on the outcome from the combination of Lemba and Pembro, but one of the main concerns from the Clinicia is the high rate of side effects in terms of discontinuation and in terms of interruption and dose modification. Then some voices, you know, show up and say that we should start with a dose reduction on Lembatinib. What is your piece of advice on that? Yeah, so I think that the concerns regarding the toxicity and the adverse events are, of course, valid. And I think it's really important to pay attention to the patient that is in front of you and the phenotype that is in front of you and their medical comorbidities. I will tell you that in Keynote 775, it was representative of the average endometrial cancer patient in terms of medical comorbidities. So endocrine issues, thyroid issues, diabetes, you know, the percentage of patients with high blood pressure was, I think, around 45%. So I think it was representative of the patients that we see in the real world. I think the toxicity that we saw with both the combination is on par with what we see, as I stated, you know, for drugs that are in these classes. I think that these drugs are here and we have to develop a comfort level. We have to develop an expertise. We have to educate our patients. They need to know what is coming and what, you know, what they should expect. Seeing patients back frequently is very helpful. But I think dose holds, dose reductions are really par for the course for drugs like lenvatinib. And I think that that's really, you know, a well-known, you know, phenomena with these class of drugs. In terms of starting at lower doses, I think that we have, you know, a phase two trial that established the overall safety of this combination. And again, no new safety signals were identified. We now have a phase three trial that has evaluated that in a large prospective way. So I think I would recommend that for the average patient, it is important to start at the recommended dose. But again, monitor patients very closely. Of course, there are exceptions. And you need to be a good doctor and take care of the patient that is in front of you. But I think I would caution, you know, people from picking random doses, you know, that have not been recommended or tested in prospective clinical trials. Thank you. I don't think that I have enough time for an additional question because I wanted to ask. It's for you. So, I mean, the data that you have presented are really amazing. The combination of myrbetuzumab platelets work in a very outstanding manner. My question for you to explain to the audience is how many patients with ovarian cancer have high folate receptor alpha? How many patients may benefit from this combination whose tumor have a high expression of folate receptor alpha? Yeah, so it's right about 40% plus minus. So, you know, I think it's really important to keep in mind, you know, we're seeing more and more in the combination therapy that the medium probably also benefits. Clearly, the high expressors benefit more. And in Katie's work, Dr. Katie Moore's work has really shown that. So, about 40%, it's going to be, you know, just under 50-50. Keep testing. You know, I think maricel study, we need to enroll that, that we want this drug available throughout the world. You know, I've said, and I will continue to say, my hope is in, particularly in those with high folate receptor alpha expression on their tumors, that myrbetuzumab will replace paclitaxel with the toxicity profile, as well as the personalized approach that we will continue to test it and make sure it's safe in the triplet, MERV, CARBO, plus minus BEV, and move forward. You know, one, I know we're down the last minute here, but, you know, Anna, thank you so much for wonderful moderation, Roberto, and everybody, just such amazing work being done by my colleagues. When we look at platinum-resistant ovarian cancer, we need to stop saying it's a, you know, 20%, 15-20% response rate. Every contemporary trial has been about 10% plus or minus, you know, and really less than 10% and single agent without BEV. And we have to get patients access to these trials because the agents that we're developing are so much more exciting than what's commercially available with PLD, TOPO, and GEMSAR. I'm sorry to say, but something to keep in mind as we move forward. Thank you. Thank you, David, for being so short. You know, we really are running out of time. Impressive session with awards before, great awards, and now very great scientific session. I'd like to thank everybody on behalf of Michael Chair, of my president, and all the audience. And if you have any question for us or any of the other speakers that you have heard here today, visit the chat rooms in the networking lounge. Thank you for joining us and enjoy the rest of the meeting. Thanks, everybody. Thank you all. Thank you. You have a great job. Thank you so much.

IGCS 2021 Annual Global Meeting

award ceremony

gynecologic cancer community

acceptance speeches

ARIEL4 trial

Rucaparib

chemotherapy

relapsed ovarian cancer

BRCA mutation

Outback trial

adjuvant chemotherapy

chemoradiotherapy

Keynote 775 trial