Immunotherapy making inroads into advanced endometrial cancer management: A single center real world experience.

Abstract

e17635 Background: Chemotherapy with carboplatin and paclitaxel was the standard treatment for advanced endometrial cancer (EC) for many years. In recent times, immunotherapy with dostarlimab (RUBY study) or pembrolizumab (NRG Gyn018 trial) in combination with chemotherapy was initially approved for mismatch repair (MMR) deficient population, and subsequently, was also approved for the MMR proficient group as 1 st line therapy. In the deficient MMR population in the RUBY study, estimated progression-free survival (PFS) at 24 months was 61.4% in the dostarlimab group versus 15.7% in the placebo group. In the proficient MMR group PFS at 24 months was 28.4% in the dostarlimab group versus 18.8% in the placebo group. We have very limited data about immunotherapy use in endometrial cancer in India. Methods: This is a single center, retrospective analysis of patients with advanced EC who received treatment with immunotherapy at our center (Manipal hospital, Bangalore). The endpoints were PFS, overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: 24 patients received immunotherapy plus chemotherapy between Dec 2020 to Dec 2024. Median age was 62 years. 14 were MMR proficient [7 endometroid carcinoma (CA), 5 high grade serous CA, 1 carcinosarcoma, 1 neuroendocrine CA] and received pembrolizumab with chemotherapy in 1 st or 2 nd line. 10 were MMR deficient [8 endometroid CA, 1 endometrial sarcoma and 1 poorly differentiated CA] and received pembrolizumab or nivolumab. MLH1 and PMS2 loss was seen in 6 patients and 4 had MSH2 and MSH6 loss. Among MMR proficient patients, at median follow-up of 10 months, median PFS was 10 months, and 1 year PFS was 30% by Kaplan–Meier estimates. Median OS was not reached, and 1 year OS was 58%. ORR was 64%, with 9(64%) partial response and 5(36%) progression. Among MMR deficient patients, at median follow-up of 20 months, median PFS was not reached, 1 year and 2 year PFS was 70% and 60% respectively. Median OS was not reached, and 2 years OS was 68%. ORR was 90% with 4 complete response (40%), 5 partial response (50%) and 1 progression (10%). Overall AEs were mainly hypothyroidism, skin toxicity and fatigue with no grade 3/4 events. Conclusions: Immunotherapy with chemotherapy is very effective in our MMR deficient EC patients, with outcomes very similar to the RUBY and NRG Gyn018 trial. MMR testing by IHC is very easy, cheap and quick, and it is imperative to identify this subgroup considering their remarkable outcome. Immunotherapy was very well tolerated in our patients. In the MMR proficient group, immunotherapy showed additional benefit compared to our historical data, but this was a modest improvement, and additional measures are needed to further improve outcomes.