Please begin. Hello, everyone. Welcome to Plenary 5. I'm Dr. David Attalla from Lebanon, moderating with Dr. Andreas Obermeier from Australia. We are honoured to be with you today. We will hear three outstanding papers. We will have time for questions and answers at the end of this session for all papers. Now the floor is open for you, Dr. Nishikawa. You have seven minutes. Hello and thank you. I'm here to talk about the JGOG 3023 trial. This phase 2 trial evaluated the efficacy and safety of bevacizumab of top of standard of care in Japanese patients with platinum resistant epithelial ovarian palpian tube or primary peritoneal cancer. Here are our disclosures. Bevacizumab has demonstrated efficacy when administered beyond status with progression in various clinical settings, including platinum sensitive recurrent cancer. However, no trials have evaluated bevacizumab beyond disease progression in patients with platinum resistant recurrent ovarian cancer. Patients with platinum resistant recurrent cancer who were previously treated with bevacizumab were randomized to single agent chemotherapy or chemotherapy plus bevacizumab. The primary endpoint was investigator-assisted progression-free survival. Patients were excluded for reasons such as ovarian borderline malignant tumor, history of other clinical active malignancy within five years of enrollment, four or more previous anticancer regimens, presence of intestinal disorder that increased risk of gastrointestinal perforation, and recent operation or radiation therapy. 103 patients were enrolled with 51 randomized to chemotherapy and 52 chemotherapy plus bevacizumab. Two patients discontinued and three received incorrect treatment. Therefore, the safety population comprised 50 patients in the chemotherapy group and 51 in the chemotherapy plus bevacizumab group. Baseline characteristics both fairly well balanced. The treatment history was also similar in both groups. About half of patients in each group had previously received bevacizumab as frontline therapy and half received bevacizumab for platinum-sensitive ovarian cancer. PLD and gemcitabine are common chemotherapy regimens in Japan. This slide shows the primary objective. Investigator assessed progression-free survival. Chemotherapy plus bevacizumab was associated with a significant increase in progression-free survival with a ratio of 0.54 versus chemotherapy alone. Progression-free survival favored bevacizumab in some subgroups of patients, including prior treatment with one or two regimens, platinum-free interval of three to six months, presence of ascites, and maximum tumor diameter. Although the maximum tumor diameter was a significant factor based on the p-value, the hazard ratio in each subgroup was not significant. As shown on this slide, there was a numerical improvement, although not statistically significant, in overall survival in favor of chemotherapy plus bevacizumab. Now our subgroup shows a statistically significant overall survival benefit of chemotherapy plus chemotherapy plus bevacizumab. The objective response rate was 25% in the chemotherapy plus bevacizumab group versus 13.7% in the chemotherapy group. Using RACIST or GICT-CJ125 criteria, there was one complete response and 12 partial responses in the chemotherapy plus bevacizumab group, and seven partial responses in the chemotherapy group. There was no difference in the response rate using the GICT-CJ125 criteria alone. There was no significant difference in the number of procedures performed. Treatment-related adverse events occurred in 96% of patients in each group. Serious adverse events, adverse events leading to treatment discontinuation, and adverse events of grade 3 or above were more frequent in the chemotherapy plus bevacizumab group. In conclusion, chemotherapy plus bevacizumab resulted in significantly longer progression-free survival, a numerical improvement in overall survival, and a greater objective response rate compared with chemotherapy alone. The number of percentages was similar in both groups. The overall incidence of treatment-related adverse events was about 96% in both groups. Our results suggest that bevacizumab beyond disease progression is an effective and tolerable treatment option for patients with platinum- resistant recurrent ovarian cancer. Here are our acknowledgments. Thank you. I would like to invite Dr. Rodney Rocconi from the USA to present his work. Dr. Rocconi, the floor is yours. All right. Okay, thank you for allowing us to present our data today. It's an honor to represent our group discussing a randomized, double-blind, placebo-controlled trial of frontline maintenance vigil immunotherapy in advanced stage ovarian cancer with an efficacy assessment on homologous recombination proficient cancers. Here are our disclosures. It is well known that cancer immunology involves transmitting antiimmune signals in order to undergo immune escape. Vigil is an autologous vaccine that is derived from a patient's cancer cells at the time of surgery and then are modified to target that patient's own cancer neoantigens. As such, each vaccine is only good for that specific patient's cancer. Additionally, this vaccine is modified to contain the actions of blocking immunosuppressive cytokines. This is achieved through a knockdown of furin and TGF beta genes. Also, increase in neoantigen MHC presentation and CD8 positive T cell activation by a granulocyte macrophage colony stimulator factor which helps recruit immune cells to the region. Thereby combining the specificity of the Vigil vaccine to neoantigens, this results in a production of a cancer neoantigen-specific immune response. Basically, we harvest ovarian cancer tumor at the time of initial surgery in chemo-naive patients. Vigil vaccine is then created to recognize tumor specific neoantigens with the previously mentioned genetic modifications. Vigil is essentially administered interdermally every four weeks for a total of four to twelve doses depending on the amount of vaccine created. It creates a more immunogenic environment where colony factors and antigen presenting cells can stimulate, recognize cancer neoantigens and present those neoantigens to T cells. Thus, this leads to an anti-tumor T cell activation and a cancer neoantigen-specific T cell response. Based on promising phase one results, we initiated this double-blinded placebo-controlled randomized phase two study of Vigil versus placebo. To be eligible, patients had to have advanced stage ovarian cancer and achieve a complete clinical response to frontline therapy. The trial was designed to detect a hazard ratio of 0.45 with a single-sided alpha of 5% and a 90% power. As such, we needed 54 recurrent events to have adequate power to detect our primary endpoint which was recurrence-free survival calculated from the completion of the patient's frontline therapy. Secondary endpoints were overall survival, safety, toxicity, and a subgroup analysis based on BRCA status. Ninety-one patients enrolled into this study with 46 in a Vigil arm and 45 in a placebo arm. Groups were similar in regards to age, stage, chemotherapy, administration, whether adjuvant or neoadjuvant, as well as residual debulking disease. However, the Vigil group did have more ECOG1 patients and fewer BRCA-mutated patients. In data presented previously at SGO earlier this year, Vigil was demonstrated to be well-tolerated with no grade 4 toxicities in the entire study, and the majority of adverse events were injection site irritation that was equal between the two groups. Additionally, in that presentation, our primary endpoint of recurrent-free survival in all patients from the completion of frontline therapy showed only a trend in the benefit of survival at a p-value of 0.065. However, the predetermined secondary endpoint of assessing BRCA-wild-type patients showed an improvement in recurrent-free survival with Vigil from 8 to 12.7 months that was significant at a p-value of 0.014. Looking at overall survival for all patients in the study, again, failed to show an overall survival benefit, but when looking specifically at the BRCA-wild-type, again, an enhanced effect was seen, demonstrating a statistically significant benefit in overall survival at a p-value of 0.02, with a 59% reduction in death compared to placebo. Although Vigil demonstrated previously a significant improvement in recurrent-free survival and overall survival, specifically in the BRCA-wild-type cohort, a significant limitation of our prior report involved a lack of correlated survival with homologous recombination status, where obviously the BRCA-wild-type group consists of both homologous recombination proficient and homologous recombination deficient tumors that are vastly different in their clinical behavior. Thus, the goal of this updated study was to specifically evaluate HR status of the 67 patients that had BRCA- wild-type tumors. HR analysis was performed using Myriad, MyChoice, and demonstrated that 25 patients, 54% of the Vigil arm, had homologous recombination proficient tumors, and 20% or 44% of the placebo, excuse me, 20 patients or 44% of the placebo arm had HR-proficient tumors. When looking at recurrent-free survival and HR- proficient tumors only, did show an improved survival from 5.7 months to 10.6 months in the Vigil arm that's statistically significant in a p-value of 0.007 and a 61% reduction in recurrence. When looking at overall survival in HR-proficient tumors, also demonstrated improved survival from 26.9 months in placebo compared to median not reached in the Vigil arm with a p-value of 0.019 and a 66% reduction in death. Restricted mean survival time has been validated as a beneficial methodology to calculate survival outcomes in immunotherapy. In our study this approach confirmed our findings with statistically significant benefit with Vigil for both recurrent-free survival with a doubling of the months from 10 to 20 in the Vigil arm, p-value of 0.022, as well as a significant benefit in overall survival with 28 to 38 months with a p-value of 0.034. So in previously presented data, this prospective double-blind placebo-controlled trial, Vigil demonstrated only a trend in its primary endpoint of all patients in recurrent-free survival. What was noteworthy in that study is the predetermined secondary endpoint that showed enhanced efficacy in the BRCA wild-type patients with improvements in both recurrent free and overall survival with maintenance in the frontline setting. For this study specifically, in HR-proficient tumors, the effect of VIGIL determined a statistically benefit in both recurrent free survival with a 61% reduction of recurrence and overall survival with a 66% reduction in death. Restricted meantime survival analysis confirmed this benefit. So thus moving forward, this novel discovery of the benefit of VIGIL on HR-proficient tumors is particularly encouraging. And despite the unquestioned benefits of PARP inhibition to ovarian cancer, it's effective overwhelmingly seen in HR-deficient tumors. Thus, we believe that VIGIL fulfills an unmet need in the HR-proficient ovarian cancer awards further study. Additionally, translational experiments are ongoing in our lab to determine predictive biomarkers that could help further stratify patients for future studies. We'd like to extend our gratitude specifically to our patients and their families and to thank all our collaborators for this exciting clinical trial. Thank you. Thank you. Thank you, Dr. Rocconi for an outstanding presentation. And I would encourage you all to submit questions through the Q&A panel at the bottom of your screen. Next up is Dr. Angeles Alvarez-Sikort, please. Good morning and hello. Thank you so much. On behalf of all my co-authors and investigators from the VILIA trial, we really appreciate the opportunity and are thankful to the IGCS committee for the opportunity to present our research. And this is not letting me forward, hang on. Let me try this. Here we go, here's our disclosures and conflict of interest. VLIPRIB is a PARP inhibitor that was evaluated in the phase three VILIA trial in women with newly diagnosed advanced stage, high grade, serious ovarian, tubal and peritoneal cancer. The schema for this trial is noted below. Eligible patients were randomized one to one to one to one of three arms, either VLIPRIB combined with chemotherapy followed by VLIPRIB maintenance or the VLIPRIB throughout arm, VLIPRIB combined with chemotherapy only followed by the placebo maintenance or the control arm, which was placebo combined with chemotherapy followed by placebo. Patients received six cycles of chemotherapy and the study drug followed by 30 cycles of maintenance therapy. The primary endpoint for this trial was presented at the ESMO meeting last year and is well published in New England Journal of Medicine article. The addition of VLIPRIB to chemotherapy followed by VLIPRIB maintenance resulted in a six month improvement and progression free survival for the whole population. Quality of life is also included in this study and included two different survey methods, the NFASI18 and the EQ5D5L. These are both validated instruments in ovarian cancer and the surveys were conducted day one, cycle one, as well as every other cycle, the final study visit and at the 30 day follow-up. The survey completion rates at the pre-specified high end points were excellent, at least 94.8% for the EQ5D5L and 97% for the NFASI18. The quality of life assessment demonstrated no significant detriment with the addition of VLIPRIB to chemotherapy. However, we really wanted to further understand the benefits and the trade-offs of therapy with regard to toxicity. In order to do this, we conducted quality adjusted progression free survival and a quality adjusted time without disease symptoms or treatment toxicity or Q-twist. Shown here are the different methodologies that we utilized. Quality adjusted progression free survival was compared specifically in the VLIPRIB throughout arm to the placebo combined with chemotherapy followed by placebo arm. This incorporated restricted mean PFS and is a product of this restricted mean PFS as well as the adjusted mean estimates of the patient utility score. From the time of randomization to disease progression. In addition, we conducted a Q-twist analysis. This is often referred to as the good time of health without disease symptoms or treatment toxicity. And we did this for the primary study arms I just mentioned in the whole population as well as two subgroups, those with HR deficient disease and another subgroup with BRCA mutations. The Q-twist was calculated and compared as a utility weighted sums of the mean durations within two health states. The time with toxicity denoted as tox and time without toxicity or twist. The toxicity we included initially for the primary assessment was nausea, vomiting and fatigue. As you know, these are well-known PARP inhibitor related class side effects that our patients often experience. We also conducted a twist analysis without adjusted for the primary study arms I mentioned. And we conducted sensitivity analyses for those using greater than or equal to grade two treatment emergent adverse events and another for those with greater than or equal to grade three treatment emergent events. Shown here are quality adjusted progression-free survival outcomes in months. The red highlighted box demonstrates that the quality adjusted PFS was longer in the VLIPRIP throughout arm, 19.5 months compared to 16.5 months for those treated with chemotherapy and placebo with a statistically significant P value of less than 0.001 and approximately three month difference. Shown here are Q-twist findings in all patients as well as the two different subgroups. Similarly, we see approximately three month improvement in Q-twist with an interval of 20.8 months for the VLIPRIP throughout arm and 18 months for those treated with chemotherapy and placebo. Including HRD and BRCA, we see longer intervals with a difference of four to five months. The P values were significant in all of these subgroups with a value of less than 0.001. This is the twist analysis and shown here is a graphical representation. This is not adjusted and this is the analysis for the whole population. Blue represents toxicity while the green represents twist. Now you can note that there's higher toxicity than we see with the maintenance PARP inhibitor arms and I think this is really due to the chemotherapy related toxicity as well. And what you can see is that there's higher toxicity state in the VLIPRIP throughout arm. And with regard to the twist analysis, there's a slight numerical increase in the VLIPRIP compared to placebo. VLIPRIP is demonstrated on the left and the placebo arm is on the right in these curves. Shown here are sensitivity analyses. The top three rows demonstrate the analysis limited to greater than or equal to grade three treatment emergent adverse events. And the lower rows are related to greater than or equal to grade two treatment emergent adverse events. The toxicity time best demonstrated in this top row here for grade three and this row here for grade two is longer in the VLIPRIP throughout arm and is statistically significant with P values of less than 0.001. The twist analysis is similar in both of these subgroups and the Q-twist demonstrates again approximately a three month improvement in this interval in both of these subgroup analysis with a statistically significant P value of less than 0.001. In conclusion, compared to chemotherapy alone, VLIPRIP added to chemotherapy and continued as maintenance had significant patient-centered benefits in terms of quality adjusted PFS and on treatment Q-twist. A significant difference in mean quality adjusted PFS of approximately three months was seen in the VLIPRIP throughout arm. Similarly, although the mean time of twist was the same in the groups, we saw an improvement in the Q-twist interval of approximately three months in the VLIPRIP throughout arm. Findings in the overall population were consistent across the biomarker subgroups and in sensitivity analysis exploring either greater than or equal to grade two treatment emergent adverse events and as well as greater than or equal to grade three treatment emergent adverse events. I'd also like to thank all the patients who participated in this study, their caregivers, the investigators and the clinical trial research teams that all the sites were participating in Valia. I also appreciate your attention. Thank you, that was an excellent presentation, Dr. Secord. Thank you very much for sharing this data with us. We are running on time, which is fantastic and we can have five minutes for Q&A. I would encourage all on this session to submit questions through the Q&A button at the bottom of your screen. I might just kick this off. Dr. Secord, was the QAPFS or the Q-twist, was that the primary study endpoint in your trial or was it a secondary endpoint? Oh, this was an exploratory endpoint. That's an excellent question. This was an ancillary data assessment and so it was not either a primary or secondary endpoint. It was something that we were very interested though because as you know, this was the trial, the only one of those trials that included a PARP inhibitor with chemotherapy followed by a PARP inhibitor maintenance. So it was important to understand those trade-offs in terms of the toxicity and the benefit of adding that drug. I'm very interested in the trade-offs of toxicity and quality of life and I really look forward to reading about your findings in the paper. Thank you. If I may just direct the question to Dr. Rocconi, if I may. Dr. Rocconi, you have shown that your trial was powered on a hazard ratio of 0.45 and you just very, very narrowly missed that in the primary study endpoint but you have shown us very impressive data in the subgroup of BRCA wild-type patients. Couple of questions. Are you planning to take this new, did you expect that this was, did you expect this finding? Expect is a little bit of a loaded word but yeah, on some previous phase one data, you know, we did see enhanced effects within the BRCA wild-type patient cohort but honestly didn't have enough to really make any definitive claims one way or the other. So that's why the phase two study did not have a biomarker specific to wild-type versus BRCA mutated into specific cohorts. So we saw it in phase one but didn't know, we didn't have enough statistical power to really determine if it was real or not, to be honest. And do you plan to follow up with a subsequent trial in this cohort of patients? We do. And, you know, I think the several questions that as we're trying to design that next step, there's also some phase one data that shows some synergy with this vaccine, with a checkpoint inhibitor that is very encouraging. So that's one possibility and still a maintenance phase of this. The other question is, you know, I think with an all comers frontline, you know, PARP maintenance that's out there, you know, do we incorporate PARP, you know, plus or minus this is also something that we're considering. But we're working through those issues right now and trying to design the best study where you get completed to answer the questions that we need to be answered. What is your hypothesis why Vigil was so effective in BRCA wild type patients and less effective in others? Yeah, excellent question. You know, I think right now, well, one thing for certain is that, you know, in the, you know, patients with BRCA mutations, that is a obviously a more heterogeneous, more genomically unstable type tumor. And we think that that leads to a more diverse clonal neo-antigen population. So it essentially creates a lot of noise, you know, on the cancer cells themselves. Whereas a, you know, HR proficient type patient or a BRCA wild type is a little more homogeneous. So I think some of it, it just is the efficiency of directing the vaccine towards the tumor specific neo-antigens. And I think there's less noise in those proficient tumors because they're allowed to repair their DNA more effectively. There's also, you know, some enhancement of MHC2 complexes that we're seeing in some of our translational work that we think might also play a part in that as well. But we're still working hard on the translational endpoints to really dig in and see what other biomarkers could be and play a part of that rationale. Thank you very much for answering my questions. Yes, sir. Thank you. I hand over to David Attala. Thank you. So we'll hear now from Dr. Gilles Friar to present the next abstract. Dr. Friar, please. Thank you, Mr. Chairman. First, I would like to thank the IGCS organizers for giving me the opportunity to present pure data in patients receiving Niravarib in the PRIMA trial. I would also like to thank Dr. Gilles Friar for giving me the opportunity to present I'm sorry, I think we have a technical issue. Oh, it's okay. All my disclosures. Well, the PRIMA trial showed that NIRAPI improves progression-free survival in patients with newly diagnosed advanced ovarian cancer that has responded to first-line platinum-based chemotherapy regardless of biomarker status. Patients' reported outcome measures have become increasingly important as they are thought to provide insight into factors that are important to patients and affect treatment choice. Here, we report novel PRO data in patients with HRD and HRP tumors from the PRIMA trial. Here's another view of the PRIMA trial design, where the primary endpoint was progression-free survival as measured by a blinded, independent central review. Initially, patients received a fixed dose of NIRAPI, 300 milligrams once a day, and in November 2017, the study was amended to give patients an individualized dose of NIRAPI, either 200- or 300-milligram dose based on their baseline body weight and platelet count. All tumor samples underwent testing for homologous recombination by the Myriad MyChoice test. This test relies on three factors, loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. According to the test, HRD tumors have BRCA mutation or a score of more than 42, and HR-proficient tumors are BRCA wild-type, and they have a score below 42. 733 patients were randomized, and at the database log on May 16, 2019, 37% of patients were still receiving NIRAPRIB, and 28% of patients were still receiving placebo. The median duration of follow-up was 13.8 months. Patient characteristics and demographics were well-balanced across each arm. Patients included in PRIMA had high risk of relapse, as you can see in the biomarker status of the patient populations. The population were as follows. 51% had HRD tumors and 35% had HRP tumors. As you can see, NIRAPRIB significantly improved progression-free survival in both the homologous recombination deficient and the overall population. Regarding the treatment emergent adverse events, NIRAPRIB safety in PRIMA is shown for the overall population. No new safety signals were identified for NIRAPRIB. The most common adverse event was reversible myelosuppression. Here we show an overview of the PRO instruments used in the PRIMA trial. Patients were given PRO questionnaires every eight weeks for the first 56 weeks, then every two weeks until the end of treatment. Patients took a PRO questionnaire at the end of the treatment and followed up at 4, 8, 12, and 24 weeks after discontinuation. The functional variant symptom index questionnaire were scored from 0 to 32, and the URTC questionnaire C30N of 28 were scored from 0 to 100. Across all instruments, higher scores indicated either worse symptoms or better functioning or quality of life, depending of what was being measured. FOSI is a validated eight-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the prior seven days using a five-point Likert scale scored from not at all 0 to very much 4. There was no difference in mean FOSI health utility index scores between niravarib and placebo in the HRD and HRP subgroups. The Kaplan-Meyers Curve for FOSI time-to-symptom worsening found no statistically significant difference between niravarib and placebo in HRD and HRP populations. URTC QLQ C30 is a 30-item health-related quality-of-life instrument developed to assess health outcome from a wide variety of intervention on a common scale. No meaningful difference in quality of life or physical function were detected between niravarib and placebo in the HRD and HRP subgroups of the time. For the ovarian cancer-specific URTC of 28 PRO instrument, we saw no meaningful difference between niravarib and placebo in the HRD and HRP subgroups over the course of the study. EQ5D5L is a validated tool that encompasses five domains scored from 1 to 5. Mobility, self-care, usual activity, pain and discomfort, and anxiety and depression used to calculate HUI, which measures overall quality of life from 0 to 1. No difference in EQ scores between niravarib and placebo were observed for the HRD and HRP subgroups. In conclusion, niravarib maintenance significantly improved EFS after response to first-line platinum-based chemotherapy regardless of biomarker status, and no new safety signals were identified. In the HRD and HRP subgroup, no relevant difference was observed using the four tools. Together, these data suggest that niravarib treatment has no detrimental effect on quality of life in this patient population. We are grateful to all patients and their families for participating in the study, as well as ANGOT and GOG, and to all the investigators who made it possible to coordinate this trial across continents. Thank you for your attention. Thank you, Dr. Freyer. We look forward to questions and answer session with you and the other presentation, the other presenters. Next, Dr. Harter will present some data from the PAOLA-1 trial. Dr. Harter, please. DHS, dear colleagues, I would like to thank you for giving me the opportunity to present you data about the efficacy of maintenance of pariv plus belvacizumab by biomarker status in clinical higher and lower risk patients with primary ovarian cancer in the PAOLA-1 trial. You can see here the disclosures of myself and my co-authors. Although all patients with newly diagnosed advanced ovarian cancer are at high risk for disease progression, factor STC stage and quality of surgical outcome impacts the risk of relapse and survival. The phase 3 PAOLA-1 angot-OV25 trial evaluated the addition of maintenance olapariv to belvacizumab in women with advanced high-grade ovarian cancer who were in response after first-line platinum-based chemotherapy plus belvacizumab. Adding maintenance olapariv to belvacizumab improved investigators' PFS compared with placebo plus belvacizumab in the ITT population. However, the patient selection PAOLA-1 was not restricted by surgical outcome. Therefore, we could conduct an exploratory subgroup analysis evaluating investigators' PFS in two clinical subgroups. So, we have now defined two different cohorts. A higher risk patient cohort, which includes phagostage 3 disease with upfront surgery and residual disease or neoadjuvant chemotherapy or phagostage 4 disease. And a lower risk patient cohort. This cohort includes patients with phagostage 3 disease, upfront surgery, and complete resection. We also looked at further analysis regarding the biomarker status in these two cohorts. Here you can see the design of the PAOLA-1 trial. Patients with successful first-line treatment including upfront or interval debulking surgery and who were in response after six cycles of carboplatin platinum-based chemotherapy plus belvacizumab. And in whom maintenance belvacizumab was planned were randomized to olapariv tablets for two years versus placebo. Primary endpoint was progression-free survival. And now we did an exploratory analysis in higher risk patients and lower risk patients defined as already explained. Here you can see the patient characteristics. So, we have run about 600 patients in the higher risk subgroup and around about 200 patients in the lower risk subgroups. The patient characteristics were well balanced regarding the usual risk criteria and baseline characteristics of patients including in such a trial. If we look for PFS in total cohort of patients with a higher risk, we could see here an improvement by six months with a hazard ratio of 0.6. If we look at patients with a lower risk with a hazard ratio of 0.46, we could improve medium PFS from 23 to around about 40 months in this cohort. If we look now at patients who were positive for tumor-PRACA mutation, we could show with a hazard ratio of 0.37 an improvement from 20 to 36 months in patients who were at higher risk. In patients who were lower risk and showed a tumor-PRACA mutation, we have a hazard ratio of 0.11, which means an improvement from two-year PFS from 44% to 96%. You have to add in addition that we randomized patients after end of chemotherapy. If you would like to make it maybe more comparable with other trials, you have to add to the 24 months around about seven months from the time of the first cycle of chemotherapy. If we look for the subgroup for HRD-positive patients, also here in the higher risk subgroup, we have a significant improvement with a hazard ratio of 0.39. And similar to the PRACA cohort, also in the HRD-positive cohort, we have seen here a substantial improvement with a hazard ratio of 0.15. And in the experimental arm, including Bevacizumab and Olaparib, we have a two-year PFS rate of 90%. If you look for the subgroup of HRD-negative patients, we were not able to show a significant benefit by the addition of Olaparib, neither in the higher risk nor in the lower risk subgroup. So please let me conclude. In POLAR-1, maintenance Olaparib plus Bevacizumab provided a PFS benefit over Bevacizumab alone in both the higher risk and lower risk subgroup. The reduction in the risk of disease progression or death was 40% in higher risk patients and 54% in lower risk patients. Median PFS increased from 50 months with Bevacizumab alone to 20 months with a combination of Olaparib plus Bevacizumab in higher risk patients, and from 23 to around about 40 months in the lower risk patients cohort. Consistent with the overall POLAR-1 population, Olaparib plus Bevacizumab provided the greatest PFS benefit over placebo plus Bevacizumab in higher and lower risk patients who were HRD-positive or had a tumor-pracker mutation. The substantial PFS improvement seen with Olaparib plus Bevacizumab in lower risk patients with tumor-pracker mutation or who were HRD-positive, the two-year PFS rate of at least 90% raises the hope of long-term benefit or even cure in this patient population. Thank you for your attention. And I would also like to thank my co-investigators in this trial, especially Ginny Kusabko for allowing me the opportunity to present here the data. Thank you. Thank you, Dr. Harter. I really liked your presentation. That was great. Now we will open the floor to questions. I would like to encourage all people on this session to submit their questions through the Q&A function, which you will find at the bottom of your screen. While we are receiving questions, I might just go ahead and ask Dr. Harter. So you have explained very nicely that this was a secondary analysis from the POLAR-1-angled OB-25 trial. How did you define pracker mutated? Was it just germline or germline mutations also? Did you also count somatic mutations? No, this was tumor analysis. So in this study, pracker mutation was defined by the tumor mutational status. We don't have the germline data from all patients, so therefore it's difficult to give an exact answer regarding the number of patients who have a germline mutation and if there are any differences. But in this study, all patients underwent a central tumor testing. Thank you. And you have shown us that in the group of HRT-negative patients, there was no benefit. How large was that group in percentage? So this was a minority of patients, about one third. We have to add that we also have a substantial number of patients in whom HRT testing was not possible. So I think it's easier to talk about patients with a pracker mutation or who were HRT-positive. This was around about 40% of the included patients. Right, because obviously these patients did not benefit from the intervention and there would be no point in exposing them to the treatment. There is a question coming in. Dr. Harte, the question is addressed to you. How do you think why the HRT-proficient patient population did not show the benefit of BAF and Olaparib? Is there a possibility that BAF negatively worked in these populations? I don't think that BAF has worked negatively, but I think we have to be aware of the fact that BAF is also active. And the PAOLA1 trial is so far the only PARP inhibitor trial with an active control. All other trials have compared to PARP inhibitor versus nothing. And so, therefore, I think the question that we should ask is, in the HRT-proficient population, maybe 12 months of Bevacizumab has the same activity like three years of a PARP inhibitor. So, therefore, I think this is a potential answer. The other potential answer is that in the PAOLA1 trial, this was just an exploratory analysis. In other trials, this was part of the primary analysis. And we have to keep in mind also that the data about the HRT testing in the trials are very, very difficult to understand. And maybe the finding is just by chance. So, we don't know. I think we have so many open questions regarding this issue, but it's difficult to give a definitive answer about this finding. Thank you so much. While we are still accepting questions through the Q&A button at the bottom of your screen, I might just take the liberty to ask Dr. Freyja. Dr. Freyja, are you still around? Dr. Freyja, in your presentation, you have shown us a rather big difference in progression-free survival between the groups. And by contrast, you were showing us that the intervention did not negatively impact on quality of life. In fact, your quality of life values were extremely similar. How do you explain that there was such a significant difference in progression-free survival and in toxicity, but no difference in quality of life? This is certainly one of the limitations we have with quality of life data and a variety of questions, because they mix, in fact, toxicity and also symptoms, which can be related to tumor progression. And at the end, it's very difficult to differentiate between those data. And we can perhaps hypothesize that toxicity and tumor progression may counterbalance themselves, explaining that we show no obvious difference at the end. But what is important, I think, is that in the maintenance phase, we don't see that potential excess of toxicity due to norepinephrine would significantly impact the overall quality of life. Thank you. I'm really thinking that we're moving more and more into composite scores, like very similar to what Dr. Secord has shown today, where we're looking into time-dependent quality of life data. Would you plan to run something similar, like a Q-twist or a QAPFS on your sample? At that time, this analysis was not made, but I think it's an interesting hypothesis to have survival analysis, which can be improved, I would say, by quality of life data, such as in the Q-twist. It's a way of seeing quality of life effects on survival, I guess. More and more, we begin to understand that patient-reported outcomes are increasingly important and relevant. So this is the background of my question. Dr. Attala, do you have any questions to the presenters? Yes, eventually for Dr. Harter. While looking at your interesting data, in low-risk patients, we may say that the effect on PFS may be due to olaparib only, because if you compare to the PFS in solo trial, they are unreached also. So in low-risk patients, maybe BEV didn't add anything compared to olaparib. Maybe the effect is olaparib. What do you think about it? I still think that this is a combination. So I have never seen data else, not from the solo one trial, with a two-year PFS rate of more than 90%. So this was for me absolutely the first time that I have seen such data in patients with advanced ovarian cancer. So therefore, I think in this subgroup, my interpretation, best treatment is the combination of bevacizumab and olaparib. But that's my personal estimation. So we don't have any randomized data comparing this to treatment strategies. Maybe olaparib alone is enough, but I think at the moment we don't know. And there were also some trial comparisons shown earlier this year between solo one and Paola one. And in the presented subgroups, it seems to be that the combination is more effective than the monochemotherapy, at least in the BRCA-positive patients, which could be compared. This was shown by Ignaz Fagot at SGO in March, I think, this year it was. And Dr. Freyer, did you encounter with the neraparib some leukemia-induced mutineraparib in your series? Yes, as it was presented at ESMO and published in the New England Journal of Medicine, we did not see any major concern with this data, which was absolutely similar to the data which were already presented and published with other PARP inhibitors. Okay. Andreas, do you have any other comments? I have no further questions at this point. Okay, thank you. Thank you. So this has been an outstanding session, and thank you for sharing your work. If you have any questions we did not have time to answer, or please feel free to contact the speakers with the IGCS link chat feature here in the meeting portal. This concludes the IGCS program, and now we'd like to welcome the Korean Society of Gynecological Oncology to commence the regional session. All viewers are welcome to stay. Thank you.

clinical trials

ovarian cancer

JGOG 3023 trial

bevacizumab

Vigil vaccine

maintenance therapy

homologous recombination proficient tumors

nirapirib

PAOLA-1 trial

combination therapies