Real-World Treatment Patterns and Survival Outcomes Among Patients With Advanced/Recurrent Endometrial Cancer Treated With Dostarlimab
Robert Coleman, MD, Texas Oncology, US Oncology, The Woodlands, TX, discusses results from a study that compared the efficacy of the anti-programmed death (PD)-1 antibody dostarlimab evaluated in the single-arm, Phase I GARNET trial with current real-world treatment.
Transcript
My name is Rob Coleman. I'm a Gynecologic Oncologist in Houston, Texas, and I serve as the Chief Scientific Officer for US Oncology Research. I also am a Gynecologic Oncologist with Texas Oncology in the Woodlands, Texas.
So the trial that I wanted to briefly speak about was a real-world evidence trial, evaluating the efficacy of dostarlimab in patients with tumors that were deficient in MMR. And we were trying to evaluate the efficacy of that single-arm trial that came from the GARNET trial against a real-world synthetic control arm of patients receiving chemotherapy that were enrolled over about a six-year period coming from a commercially available database. And so the point here was that we had had quite a bit of experience looking at the role of immune checkpoint inhibitors, in this case dostarlimab, in women whose tumors were deficient in the MMR proteins. So we knew that there was efficacy signal, but the question is, how much of a signal?
And so to provide some context, we'd constructed using this inverse probability weighted design to develop a control arm where we could reduce the bias for the selected therapy for these patients that were treated at centers around the United States and come up with a somewhat unbiased control arm that was recruited basically in the same time point that the GARNET trial was being run. So the concept here is that we were able to take the results of this study and then to create a control arm that was stripped of the confounding co-variants. And there's a mathematical algorithm to help do that.
And so what we did is we showed that there was this very strong treatment effect, as we expected between, what we saw in the GARNET experimental arm and this externally constructed control arm. Now, a lot of people say, well, what about the MSI status or the DMMR status of the control arms? And it's a really good question. It was one of my major concerns about doing this trial. But one of the things that came to me was that in the patients that were treated with chemotherapy, the presence or absence of this deficient MMR status and the tumors didn't seem to matter with respect to the efficacy of chemo.
So it's a predictive biomarker for the use of an immune checkpoint inhibitor, but it doesn't seem to have either a negative or positive factor on the expectation for outcome of chemotherapy, which made this control arm actually relevant. So although it's hypothesis generating, it does provide us with some context with how strong the efficacy signal was seen with dostarlimab in these patients whose tumors were deficient in mismatch repair.
Thank you so much for giving me the opportunity to speak about this project.
