743P - Immunotherapy plus chemotherapy in the first-line treatment for primary advanced or recurrent endometrial cancer: An extracted individual patient data and trial-level meta-analysis

Background

Immunotherapy (IO) plus chemotherapy (CT) with maintenance IO has emerged as a new standard first-line treatment for primary advanced or recurrent endometrial cancer (EC) in patients (pts) with deficient DNA mismatch repair (dMMR). For those with mismatch repair–proficient (pMMR) disease, progression-free survival (PFS) magnitude of benefit is smaller, and an overall survival (OS) improvement has not yet been demonstrated. This meta-analysis aims to evaluate the PFS and OS in dMMR and pMMR pts with EC.

Methods

We searched PubMed, Embase, Cochrane and oncology meetings until April 2024. Randomized phase II or III trials (RCTs) investigating IO plus CT in first line for EC were selected. A meta-analysis of extracted individual patient (pt) data (eIPD) was performed. IPD was reconstructed from reported Kaplan-Meier plots through WebPlotDigitizer and the R package IPDfromKM and further combined. A trial-level meta-analysis was also conducted using fixed and random effects models.

Results

Five RCTs were included (NRG-GY018, RUBY, MITO END-3, AtTEnd/ENGOT-en7, DUO-E). 2436 pts were included in PFS analysis: 621 in PFS dMMR (318 in IO arm versus 303 in control arm) and 1815 in PFS pMMR (978 in IO arm and 837 in control arm). In the trial level meta-analysis, both subgroups derived PFS benefit with the addition of IO (dMMR: HR 0.34, 95% CI 0.27-0.44; pMMR: HR 0.77, 95% CI 0.63-0.95). 2317 pts were included in OS analysis: 560 pts in OS dMMR (290 in IO arm and 270 in control arm) and 1757 pts in OS pMMR (947 in IO arm and 810 in control arm). In the trial level meta-analysis, IO improved OS only in the dMMR group (dMMR: HR 0.39, 95% CI 0.27-0.56; pMMR: HR 0.87, 95% CI 0.74-1.02). The results in the eIPD analysis yielded similar results with better outcomes in PFS for all subgroups, with a 3-year absolute gain of 36% in dMMR and 6% in pMMR. An absolute 3-year gain of 28% was observed in OS in the dMMR pts.

Conclusions

IO should be part of the standard of care in first-line for dMMR EC. For pMMR tumors, the clinical relevance of IO was limited, and longer follow-up is warranted. Molecular classification exploratory analysis from these trials can help us to understand who are the pMMR pts that benefit from IO.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.C. Gouveia: Financial Interests, Personal, Invited Speaker: Novartis. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Karyopharm, Merck, Zailab, BioNTech, Daiichi Sankyo, Eisai, ImmunoGen/AbbVie, Incyte, Regeneron; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, Ultimovacs, Apexigen; Financial Interests, Institutional, Trial Chair: Deciphera; Non-Financial Interests, Advisory Role: Ultimovacs; Non-Financial Interests, Member, Member of Prix Galien Awards Committee: Prix Galien Foundation. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, ImmunoGen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, ImmunoGen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other Grants for traveling: AstraZeneca, Clovis Oncology, GSK. R. Colombo Bonadio: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Adium Pharma, AstraZeneca, Pfizer, Nestle health science, Daiichi Sankyo, BMS, Gilead Sciences; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca; Other, Travel, Accommodations, Expenses: Daiichi Sankyo, AstraZeneca, MSD. M. Scaranti: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Gilead; Financial Interests, Personal, Principal Investigator: AstraZeneca, Libbs, Amgen, Sophia genetics. All other authors have declared no conflicts of interest.