51成人动漫

Immunotherapy combined with standard chemotherapy significantly improved progression-free survival in patients with advanced or recurrent endometrial cancer, according to results from two randomized phase III trials presented at the Society of Gynecologic Oncology annual meeting.

In this exclusive 51成人动漫 video, , medical director of Gynecologic Oncology at the U.S. Oncology Network and professor on the Clinical Scholar Track in the Department of Obstetrics and Gynecology at the University of Arizona College of Medicine in Phoenix, offers a deep dive into the results and clinical implications of the and trials.

Following is a transcript of his remarks:

Greetings. My name is Brad Monk. I'm a gynecologic oncologist from Phoenix, Arizona, and I just returned from Tampa, Florida, for the Society of Gynecologic Oncology.

And if you haven't heard, the world changed. The world changed based on GOG Foundation-sponsored trials. Now, as you know, the GOG Foundation has two components: NRG, sponsored by CTEP, the Cancer Therapy Evaluation Program; and GOG Partners, which works exclusively with pharma but also sponsors their own trials. So NRG, GOG Partners -- both part of the Foundation.

It's my pleasure to be vice president of the Foundation, co-director of Partners, but it's one house, one opportunity. And both parts of the house reported simultaneously on March 27, 2023, and published in the New England Journal two transformational studies which are changing the landscape in newly diagnosed advanced and recurrent endometrial cancer.

Why is this important? This is important because endometrial cancer is the only gynecologic malignancy that is increasing in numbers and soon will become the most fatal gynecologic malignancy, surpassing ovarian cancer.

Now there were two complementary studies, and I say complementary because it's not competitive. The only competition is us, but most importantly our patients, against the cancer. It's not one immune checkpoint inhibitor versus another. But there was an NRG trial entitled GY018, which I'm going to call 18, and a GOG Partners trial with dostarlimab [Jemperli], called RUBY. So 18 studied pembrolizumab [Keytruda] and RUBY studied dostarlimab. And those trials added either pembrolizumab or dostarlimab to carboplatin-paclitaxel in patients at high risk for recurrence.

Now these studies were different but complementary, and whatever deficiency one of the studies has, the other one makes up for. Isn't that great?

Let me give you an example: 18 was 816 patients, which studied two separate cohorts. Now we all know that immune therapy works the best in patients who are MSI [microsatellite instability]-high or mismatch repair [MMR]-deficiency. So, 18 NRG studied one group of patients, 225 dMMR [deficient mismatch repair] MSI-high patients and then separately studied pMMR [proficient MMR] microsatellite stable, 591. Together, 816 patients, 18 funded by CTEP.

Now the other study -- smaller, perhaps even more efficient, study -- added dostarlimab. Now this a hierarchical decision. So first they looked at dMMR and then they looked at all-comers. And although not prespecified, they also looked at microsatellite stable or proficient mismatch repair. And the bottom line is yes, that when immune therapy is added to chemotherapy in newly diagnosed advanced or recurrent endometrial cancer, there is a statistically significant and clinically important benefit without any new safety signals.

And we're gonna cure some patients. We're gonna cure some patients [with cancers] that heretofore were uniformly lethal, particularly in the mismatch repair deficient subset.

Let me give you some numbers here. In the dMMR subset in GY018, the hazard ratio was 0.30 -- 70% reduction. The complementary study, which adds confidence to that sensational result is RUBY, which uses dostarlimab, and the hazard ratio there is 0.28.

So really we need -- today -- if we can get it reimbursed, I think that there will be a momentum tidal wave, because they're both published in the New England Journal on March 27, of adding pembrolizumab or dostarlimab to chemotherapy in the dMMR subset.

Now that's only about 25% of the population. So in the patients that do not have a mismatch repair deficiency -- that is, pMMR or MSS [microsatellite stable] -- it still works. So again, 18 had a separate cohort, 591 patients, and the hazard ratio for progression in the pMMR subset in 18, CTEP, was 0.54. Wow.

Now you say, look, 18 was stopped early because it was so amazing. Okay, well, RUBY went longer. The follow-up for RUBY was longer. The follow-up for RUBY was 2 years, when in 18 it was 1 year. And in fact, in RUBY we're beginning to see survival information. So not only is the hazard ratio supportive for pMMR, but in RUBY with longer follow-up, we're beginning to see survival. And many of these survival differences are not reached. So at 38.5% maturity, the hazard ratio for dMMR is also 0.3 for survival. And we're seeing in the intent-to-treat analysis that the hazard ratio is 0.64.

So it works in all-comers; it works better in the dMMR, still works in the pMMR. And I get it that GY018 studied the cohort separately, but the shorter follow-up RUBY did a hierarchical testing dMMR first, and then all-comers still hit in progression-free survival in all subsets. But because RUBY has longer follow-up, we're seeing survival.

So it's not one checkpoint inhibitor against another, it's you and me and our patients against the cancer. And in RUBY, they showed that not only was there no new safety signals, but the quality of life, the patient-reported outcomes, had a trend of doing better. So patients are not only living longer, but they're living better. Isn't that why we get up every day?

So read those two manuscripts. You can download them for free in the New England Journal on March 27, 2023. And if appropriate, please begin to add immune checkpoint inhibitors to those women battling advanced or recurrent endometrial cancer when they would otherwise just receive carboplatin-paclitaxel alone.

Thank you. Thank you to the patients, thank you to you as investigators, and share this with your colleagues because this is transformational and practice changing. And thank you to the GOG Foundation NRG018, and GOG Partners RUBY.

Thank you.

Comment