Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.

Date publication

novembre 2023

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BARTHELEMY Philippe , Pr GHIRINGHELLI François , Dr MANSI Laura

Tous les auteurs :
Buisseret L, Loirat D, Aftimos P, Maurer C, Punie K, Debien V, Kristanto P, Eiger D, Goncalves A, Ghiringhelli F, Taylor D, Clatot F, Van den Mooter T, Ferrero JM, Bonnefoi H, Canon JL, Duhoux FP, Mansi L, Poncin R, Barthélémy P, Isambert N, Denis Z, Catteau X, Salgado R, Agostinetto E, de Azambuja E, Rothé F, Craciun L, Venet D, Romano E, Stagg J, Paesmans M, Larsimont D, Sotiriou C, Ignatiadis M, Piccart-Gebhart M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/37919269

Résumé

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.

Mots clés

Humans, Female, Carboplatin, therapeutic use, Triple Negative Breast Neoplasms, pathology, Antineoplastic Agents, therapeutic use, Paclitaxel, therapeutic use, Antineoplastic Combined Chemotherapy Protocols, adverse effects

Référence

Nat Commun. 2023 11 2;14(1):7018