Okay. All right. So, we're just going to talk about two of the recent cervical cancer trials. Okay. So, just briefly, in terms of locally advanced cervical cancer, cervical cancer is the fourth most common cancer in women worldwide, and still five years of these free survival is about 68 percent, and overall survival is 74 percent. Obviously, this differs based off of initial stage of diagnosis, an advanced stage in lymph node involvement, and we know contributes to a worse prognosis. So, locally advanced cervical cancer is treated with concurrent chemoradiation therapy, and this standard of care, in terms of the chemo that's used and the radiation, has not really changed for over 20 years. Yes, there are different, you know, newer radiation modalities, but the general standard of care hasn't really changed. So, the Outback trial was a wishful thinking trial, and we were hoping that the addition of adjuvant chemotherapy to standard of care chemoradiation for these patients with locally advanced cervical cancer would improve outcomes, but it did not show that. And so, five-year overall survival in the Outback experimental trial with the addition of adjuvant chemo was 72 percent versus 71 percent in the standard of care trial, and the progression-free survival also was not significant, 63 versus 61 percent. So, the GTIG interlace trial was looking to see, well, okay, adjuvant chemotherapy didn't really work well, but would weekly induction chemotherapy prior to standard chemoradiation make a difference? And so, this included squamous adenocarcinoma and adenosquamous histologies. They used the FIGO 2008 staging, and the inclusion criteria were stage 1b1 with the node positive, 1b2 stage 2, stage 3b, and stage 4a. And patients, oh, that's interesting, two patients were randomized, I'm sorry, one-to-one to either, it was supposed to say standard chemoradiation therapy with five weeks of cisplatin versus induction chemotherapy with six weeks of carboplatin AUC2, I'm sorry, and Paclitaxel 80 milligrams per meter squared, followed by, I'm sorry, I think I missed there, yeah, and Paclitaxel 80 milligrams per meter squared, followed by chemoradiation therapy, which started in week seven. And so, they recruited 500 patients from 32 centers in five countries. The median age of these patients was 46 years, and these are some of the important clinical factors of the patients that were enrolled. So, 86% were stage 1 to 2. There were 11% that were stage 3b, and only 3% that were stage 4a. 57% were node negative. 82% had a squamous subtype, and 92% of the patients who were in the induction chemotherapy group received at least five cycles of the carboplatin Paclitaxel. And so, there was a median follow-up of 64 months, and five-year progression-free survival in the experimental arm with the induction chemotherapy was 73% versus 64% with chemoradiation therapy alone, and the hazard ratio was 0.65. The five-year overall survival was 80%, again, in the experimental arm versus 72% with chemoradiation therapy alone. So, that was very exciting where induction chemotherapy did show an improvement in progression-free and overall survival, and they had long-term follow-up. So, I just wanted to contrast this with Keynote A18. So, ELSBAC, again, had looked at adjuvant chemotherapy with standard of care. Keynote A18 was looking at, well, can we enhance the effect of chemotherapy by using immunotherapy? So, again, it included squamous adeno and adenosquamous histologies. They used the FIGO 2014 staging, and it was stage 1B, 2 to 2B node positive, or stage 3 to 4A, and these patients were randomized one-to-one to either, again, chemoradiation alone or the addition of Pembrolizumab, 200 milligrams every three weeks for five cycles concomitant with the chemoradiation therapy, and then 400 milligrams Q6 weeks for 15 cycles. And this was a much larger study. There were over 1,000 patients enrolled with the median age of 49.5 years, so similar to interlace, and 598 patients. So, over half of these patients had stage 3 to 4 cervical cancer at their intake. So, this is a little bit of a different group than interlace, where interlace, where the vast majority were actually stage 1 to 2, Keynote A18 had patients, the vast majority were stage 3 to 4. And in this group, 60% had positive pelvic lymph nodes, another 2% had positive periodic lymph nodes, and, again, the vast majority were squamous subtype. So, Keynote A18 just seemed to have a higher risk population than the interlace study did. The median follow-up, however, for this is just 17.9 months so far. So, the Pembrolizumab arm had a 67.8% 24-month progression-free survival versus 57.3% in the placebo arm, and the overall survival data is not yet mature, but there was a favorable overall survival trend. So, I just wanted to, like I said, it was a brief presentation because I wanted to discuss this because I thought that that's something that we can start, that would be helpful, especially in lower resource settings, potentially, because I know that sometimes, I have heard that it's gotten better, but in Uganda, there can be a little bit of a wait for radiation treatment. So, this is, you know, the weekly induction chemotherapy may be a potential option to improve survival for these patients while you're awaiting the radiation treatment as well. But I opened the floor to discussion because I'm excited that we have a lot of people to discuss this.

cervical cancer trials

Outback trial

GTIG interlace trial

immunotherapy

chemotherapy