Pembrolizumab/Chemo Improves Responses in dMMR/pMMR Endometrial Cancer

The phase 3 NRG-GY018 trial (NCT03914612) produced an improvement in progression-free survival (PFS), as well as objective response rate (ORR) and complete responses (CR), in patients with stage III or IVA, stage IVB, or recurrent endometrial cancer after receiving the treatment of pembrolizumab (Keytruda) with carboplatin and paclitaxel, according to Ramez N. Eskander, MD.¹

In a conversation with CancerNetwork^®, Eskander, a gynecologic oncologist and assistant professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Diego Health, discussed the results of treatment in the cohorts of patients with both mismatch repair deficient (dMMR) disease and mismatch repair proficient (pMMR) disease.

In the dMMR population, patients treated with the pembrolizumab combination achieved an ORR of 82% (95% CI, 72%-89%) compared with 71% (95% CI, 60%-80%) in the placebo arm (odds ratio [OR], 1.83; 95% CI, 0.92-3.66). Investigators reported a partial response (PR) rate of 50% vs 55% and a CR rate of 32% vs 15% in the pembrolizumab and placebo arms, respectively.

The ORR in the pMMR population was 71% (95% CI, 64%-77%) in the pembrolizumab cohort vs 58% (95% CI, 52%-65%) in the placebo cohort (OR, 1.74; 95% CI, 1.18-2.58). Each respective arm achieved a PR rate of 56% vs 50% and a CR rate of 15% vs 8%.

Transcript:

When we presented the ORR rate data for the first time, it was after we had reported the primary efficacy analysis for PFS in both populations. It is important to recognize that the PFS end point was reached at the first interim analysis when we completed accrual to both the dMMR and pMMR endometrial cancer patient cohorts. We had at least 50% of [PFS] events. Those results were presented and then simultaneously published [in the New England Journal of Medicine] showing strong benefit to the addition of pembrolizumab to chemotherapy that was both clinically and statistically significant in the dMMR and pMMR patient populations.² Subsequently, we looked at those patients who were enrolled in a trial with measurable disease so that we could look at the ORR. What we saw was there was also an improvement in the ORR for both the dMMR and the pMMR patient populations. What was provocative for us was that we saw a doubling of the CRs from 15% to 32%, in the dMMR population, and from 8% to 15%, in the pMMR population. Not only did we see an improvement in the ORR, but we saw a doubling of the CRs. One of the things that I thought was most important was when you looked at the waterfall plots for the responses in these patients, you saw that it was not driven by a small subset of patients in either of these cohorts. You saw that the benefit was distributed almost uniformly across the subjects who achieved a response to the study-directed therapy, meaning the addition of pembrolizumab to chemotherapy. This highlighted the fact that this benefit was distributed throughout patients, and that was reflected in the improvement in the ORR and then the doubling of the CRs.

References

1. Eskander RN, Sill MW, Beffa L, et al. SEMINAL: Pembrolizumab versus placebo in addition to carboplatin and paclitaxel for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: the phase 3, NRG GY018 study. 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS). November 5-7, 2023; Seoul, South Korea.
2. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/nejmoa2302312