Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND

Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy.

METHODS

MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III-IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m

FINDINGS

From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2-29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7-12·1) in the standard group and 9·6 months (7·2-17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65-0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3-4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]).

INTERPRETATION

Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted.

FUNDING

Pfizer.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests SP received grants or contracts from Pfizer and personal honoraria from AstraZeneca, MSD, Roche, GSK, and Clovis. GS received grants or contracts from MSD; consulting fees from TESARO Bio and Johnson and Johnson; and personal honoraria from Clovis Oncology. UDG received personal honoraria from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Eisai, Janssen, MSD, Pfizer, Ipsen, and Roche; and support for attending meetings or travel support (or both) from Janssen, Bristol Myers Squibb, and Ipse. CDA received consulting fees from Novartis, GSK, and Eli-Lilly; personal honoraria from Novartis, Pfizer, GSK, Eli-Lilly, and Seagen; and support for attending meetings or travel support (or both) from Seagen, Gilead, Pfizer, and Ipsen. DP received personal honoraria from Clovis and GSK; and support for attending meetings or travel support (or both) from Pierre Fabre Pharma. VS received consulting fees from Novocure, MSD, AstraZeneca, and GSK; personal honoraria from Novocure, MSD, AstraZeneca, and GSK; support for attending meetings or travel support (or both) from GSK and PharmaMar; and personal payment for an advisory board from MSD, Novocure, AstraZeneca, and GSK. AF received personal honoraria from AstraZeneca, GSK (Tesaro), and Clovis; travel grants from Astellas, MSD, and Bayer; and personal payment for an advisory board from Janssen, GSK (Tesaro), and AstraZeneca. DL received consulting fees from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen, and PharmaMar; personal honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, and PharmaMar; payment for expert testimony from Clovis; travel grants from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK; personal payment for an advisory board from Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro, AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar, and Gynecologic Cancer InterGroup for being a member of the board of directors; and institutional grants for research activities from AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, PharmaMar, Seagen, Immunogen, Novartis, Roche, and Incyte. FP received institutional financial support for clinical trials promoted by the National Cancer Institute of Naples from Roche, Bayer, AstraZeneca, Pfizer, Incyte, GSK (Tesaro), and Merck; and personal honoraria from Bayer, Pierre Fabre, AstraZeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, Roche, and Pfizer. All other authors declare no competing interests.