The phase 3 NRG GY018 trial added immunotherapy to chemotherapy in patients with recurrent endometrial cancer, regardless of mismatch repair deficient or proficient disease status, according to Ramez N. Eskander, MD.
The phase 3 NRG-GY018 trial (NCT03914612) aimed to test the benefit of adding pembrolizumab (Keytruda) with carboplatin and paclitaxel in patients with stage III or IVA, stage IVB, or recurrent endometrial cancer, according to Ramez N. Eskander, MD.
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 assessment of this treatment in patients with both mismatch repair deficient (dMMR) disease and mismatch repair proficient (pMMR) disease.
NRG GY018 was designed as a phase 3, double-blind clinical trial examining the therapeutic benefit of adding pembrolizumab to standard-of-care carboplatin and paclitaxel and then continued as maintenance vs placebo plus carboplatin and paclitaxel with placebo maintenance. Maintenance was for up to 2 years. The trial was designed specifically to adjudicate the benefit of adding immunotherapy in patients with advanced stage or recurrent disease in 2 separate patient populations: the dMMR, or mismatch repair deficient population, and the pMMR, or mismatch repair proficient population. The reason that we intentionally looked at these patient cohorts separately is because we know that, biologically, there was a strong rationale for the benefit of immunotherapy in the dMMR [population].
We wanted to independently assess the benefit in the pMMR population. The hypothesis was that, if you give cytotoxic chemotherapy, as we’ve seen in other solid tumors like lung cancer, you may be able to augment the response to immunotherapy in a disease that doesn’t respond well to immunotherapy alone: pMMR endometrial cancer. That’s because cytotoxic chemotherapy can be immunogenic on its own. It can increase neoantigen presentation. It can reduce myeloid-derived suppressor cells or regulatory T-cell activity. There are multiple hypotheses about why combining these would be beneficial. The trial was conducted to help us determine whether or not there would be a therapeutic benefit to adding immunotherapy to chemotherapy in both of these patient cohorts.
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.