Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial.
Fiche publication
Date publication
juillet 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BENGRINE-LEFEVRE Leila
Tous les auteurs :
Ray-Coquard IL, Savoye AM, Schiffler C, Mouret-Reynier MA, Derbel O, Kalbacher E, LeHeurteur M, Martinez A, Cornila C, Martinez M, Bengrine Lefevre L, Priou F, Cloarec N, Venat L, Selle F, Berton D, Collard O, Coquan E, Le Saux O, Treilleux I, Gouerant S, Angelergues A, Joly F, Tredan O
Lien Pubmed
Résumé
This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC.
Mots clés
Humans, Antibodies, Monoclonal, Humanized, therapeutic use, Female, Middle Aged, Aged, Neoadjuvant Therapy, methods, Carboplatin, therapeutic use, Antineoplastic Combined Chemotherapy Protocols, therapeutic use, Paclitaxel, therapeutic use, Chemotherapy, Adjuvant, methods, Adult, Ovarian Neoplasms, drug therapy, Cystadenocarcinoma, Serous, drug therapy, Progression-Free Survival, Cytoreduction Surgical Procedures, Neoplasm Staging
Référence
Nat Commun. 2024 07 16;15(1):5931