736P - Exceptional clinical benefit (ECB) from immune checkpoint inhibitors (ICIs) in mismatch-repair deficient (MMRd) in recurrent /metastatic endometrial cancer (r/mEC): Are we curing a subset of MMRd EC patients (pts)?

Background

ICIs have transformed the treatment landscape of MMRd m/rEC. Many pts show prolonged response even after ICI discontinuation, hinting at the potential of cure. Among MMRd EC pts with ECB from ICI, we sought to describe long-term outcomes, especially in pts who stopped ICI for reasons other than progression (PD).

Methods

This retrospective, multicenter (8 centers in France, Italy and Spain), observational study aimed to characterize pts with MMRd r/mEC treated with ICIs achieving ECB, defined as event-free survival (EFS) ≥24 months (m) and their subsequent long-term outcomes. Clinicopathological data and outcomes of pts treated from 2016-2022 were collected. Subsequent EFS (sEFS) rate (primary endpoint) was calculated from the 24-m timepoint onwards. Duration of treatment (DOT), overall response rate (ORR) calculations, and multivariable analysis for sEFS were conducted.

Results

A total of 54 MMRd r/mEC pts with ECB from ICIs were identified. Most of pts had endometrioid carcinoma (93%), MLH1 methylation (83%), recurrent disease (76%), no visceral disease (87%), and prior carboplatin-paclitaxel (68%). Overall, 78% and 19% of pts received ICIs in the second/third- or first-line setting, respectively. Anti-PD-(L)1 monotherapy was the most common regimen (91%). ORR was 98% with 50% of complete response (CR). At data cut-off, 81% had stopped ICI for reasons other than PD: per protocol (50%), toxicity (26%) or other (5%), and only 11% remained on ICI. With further median follow-up beyond the 24m mark of 21m (95%CI 8-26), only 4 pts had PD. The estimated 36m sEFS rate was 87% despite most pts had discontinued ICI. Among the 27 pts in CR, the 36m sEFS was 87.4%. Among 14 pts discontinuing due to toxicity, with a median DOT of 16m, 36m sEFS rate was 100%. In a multivariable analysis, no significant sEFS differences were observed across subgroups, including treatment line, MLH1 methylation or visceral disease.

Conclusions

Among pts with MMRd r/mEC treated with ICIs achieving ECB, the risk of subsequent relapse is remarkably low, even after ICI discontinuation. While our data require confirmation, this raises the intriguing possibility of cure.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy Institute of Oncology.

Funding

Has not received any funding.

Disclosure

J.F. Grau Béjar: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Other, Educational Activities: AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: GSK. L. Musacchio: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: GSK. O. Le Saux: Financial Interests, Personal, Advisory Board: Novartis, MSD, GSK; Financial Interests, Personal, Invited Speaker: Lilly, AstraZeneca, Clovis; Financial Interests, Institutional, Trial Chair: Novartis, Hospira-Pfizer foundation, Astellas. R. Sabatier: Financial Interests, Personal, Other, Consulting: GSK, MSD; Financial Interests, Personal, Invited Speaker: Eisai, Clovis Oncology, GSK; Financial Interests, Personal, Advisory Board: Seagen Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Other, Travel fees: MSD, Novartis; Non-Financial Interests, Other, Congress fees: GSK. C. Garcia Duran: Financial Interests, Institutional, Invited Speaker: MSD-AstraZeneca, GSK; Financial Interests, Institutional, Other, Educative activity: EISAI; Financial Interests, Personal, Other, Travel expenses: GSK, AstraZeneca. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabre, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen, Eisai; Financial Interests, Institutional, Advisory Board: Exactscience, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Coordinating PI: AstraZeneca, Seagen; Financial Interests, Local PI: msd, Daiichi; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi, MSD. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca & MSD, Olympus Europa, GSK, AstraZeneca & MSD, Olympus Europa; Financial Interests, Personal, Advisory Board, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Coordinating PI, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Coordinating PI, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Coordinating PI, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Coordinating PI, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Coordinating PI, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Coordinating PI, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. I. Ray-Coquard: Financial Interests, Personal, Advisory Board: Adaptaimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, EQRX, Eisai, GSK, ImmunoGen, Macrogenics, Merck Sereno, Mersana, Novartis, Oxnea, PMV Pharma, Roche, Seagen, Sutro; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, Translational Research NEOPEMBROV TRIAL: MSD; Non-Financial Interests, Personal, Other, President: GINECO; Non-Financial Interests, Personal, Other, Principal Investigator: PAOLA-1. 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 insitutional 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. A. Oaknin: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, F. Hoffmann-La Roche, GSK, Genmab, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Novocure, OncoXerna Therapeutics, Inc, PharmaMar, Regeneron, Shattuck Labs, Seagen/Pfizer, Sutro Biopharma, Exelisis, Daiichi Sankyo, Debiopharm International, Myriad Genetics, Zentalis; Financial Interests, Personal, Other, Travel and accommodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc, Eisai Limited Ltd, F. Hoffmann –La Roche LTD, ImmunoGen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Leadership Role, ESMO Gyn Co-Chair 2023 - 2025: ESMO; Non-Financial Interests, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape; Financial Interests, Personal, Writing Engagement, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE Immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Member: GCIG. All other authors have declared no conflicts of interest.