Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Background

In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives

The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

Design

RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.

Methods

Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.

Results

The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.

Conclusion

The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.

Trial registration

NCT03981796.

Safety of dostarlimab plus carboplatin-paclitaxel compared with carboplatin-paclitaxel in primary advanced or recurrent endometrial cancer For many years, patients with primary advanced or recurrent endometrial cancer were treated with chemotherapy, specifically with a combination of carboplatin and paclitaxel. Recently, new treatments called immune checkpoint inhibitors have been used to treat endometrial cancer. Dostarlimab, an immune checkpoint inhibitor, is being tested to treat many types of cancer, including endometrial cancer. In the RUBY trial, a combination of dostarlimab plus chemotherapy was compared with chemotherapy alone as treatment for primary advanced or recurrent endometrial cancer. Results showed that patients treated with dostarlimab plus chemotherapy had a lower risk of their cancer becoming worse and a lower risk of dying. Results in this article describe the safety of dostarlimab plus chemotherapy compared with chemotherapy alone. All patients in the RUBY trial experienced at least one adverse event (an undesired effect that happens while receiving treatment or shortly after stopping treatment); most were determined to be caused by the cancer treatments. No differences in the frequency of the overall cancer treatment-related adverse events were seen in patients who received dostarlimab plus chemotherapy compared with those patients who received chemotherapy alone. Some patients experienced an immune-related adverse event. These are a specific type of undesired effect that can occur when patients are treated with immune checkpoint inhibitors. Immune-related adverse events occurred more frequently in patients who received dostarlimab plus chemotherapy than in those who received chemotherapy alone. Physicians were generally able to treat the immune-related adverse events, and only a low percentage of patients discontinued treatment because they experienced an immune-related adverse event. The types of adverse events seen were similar to a combination of those seen in patients who received dostarlimab alone or patients who received chemotherapy alone as treatment for endometrial cancer. Dostarlimab plus chemotherapy is a new standard of care for patients with primary advanced or recurrent endometrial cancer.

Informations de copyright

© The Author(s), 2024.

Déclaration de conflit d'intérêts

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Au. reports advisory board fees from GSK and MSD. M.A.P. reports grants/research support from GSK and honoraria/consultation fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, and Merck. J.B. reports honoraria from GSK. D.Ba. reports GSK study site funding for the RUBY trial; consulting fees from AstraZeneca, GSK, and MSD; participation on a data safety monitoring board or advisory board for AstraZeneca, GSK, and MSD; and leadership in the AGO study group. R.L. reports advisory board participation from Eisai and GSK. D.B. reports institutional grants from AbbVie, AstraZeneca, Clovis Oncology Inc., Genentech, MSD, and Tesaro. L.G. reports institutional grants from Alkermes, AstraZeneca, Corcept Therapeutics, Esperas, GOG Foundation, GSK, ImmunoGen, IMV, K-Group Beta, Merck Sharp & Dohme, Mersana Therapeutics, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Shattuck Labs, Sutro BioPharma Inc., and Tesaro; consulting fees from GSK and Merck; honoraria from GSK and Merck; travel support from EndomEra, GSK, Merck, and Zentalis; and participation on a data safety monitoring board or advisory board from CanariaBio, Corcept, Eisai, GSK, Immunogen, Kora Healthcare, and Merck, and Novocure. A.Se. reports honoraria from Eisai, GSK, Johnson & Johnson, and Merck and participation on a data safety monitoring board or advisory board from Eisai and GSK. B.S. reports consulting fees from Aadi Biosciences, AstraZeneca, BioNTech, Clovis Oncology, Eisai, Genentech, Genmab, Gilead, GSK, Incyte, Karyopharm, Merck, Novartis, Novocure, Regeneron, and Seagen and payment or honoraria from Seagen. R.C. reports grants or contracts from AstraZeneca, Clovis, Genelux, Genmab, Immunogen, Merck, and Roche/Genentech; consulting fees from AbbVie, Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, Novocure, Merck, OncoQuest, OncXerna, Regeneron, and Roche/Genentech; honoraria from AstraZeneca, Clovis, Merck, and Roche/Genentech; and participation on a data safety monitoring board or advisory board from Eisai/BMS and VBL Therapeutics. A.St. reports royalties as an UpToDate reviewer. B.P. reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Duality Bio, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Seagen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, BioNtech, Clovis Oncology, Eisai, GOG Foundation, Lily, Merck, Mersana, SeaGen, Sutro Biopharma, Tesaro/GSK, Onconova, and Toray; and travel support from GSK and BioNtech. L.W. reports speakers’ bureau fees from Astra Zeneca, Eisai, Immunogen, Merck, and Seagen; and advisory board fees from AstraZeneca, Immunogen, and Seagen. M.R.M. reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zailab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). A.Ar., E.F., G.R., I.P., K.R., L.M.L., M.T., N.N., S.G., S.Sh., T.S., and V.S. have nothing to report. G.A., C.D., and S.St. are GSK employees.