Fiche publication
Date publication
janvier 2021
Journal
Nature medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARTHELEMY Philippe
Tous les auteurs :
Bachelot T, Filleron T, Bieche I, Arnedos M, Campone M, Dalenc F, Coussy F, Sablin MP, Debled M, Lefeuvre-Plesse C, Goncalves A, Reynier MM, Jacot W, You B, Barthelemy P, Verret B, Isambert N, Tchiknavorian X, Levy C, Thery JC, L'Haridon T, Ferrero JM, Mege A, Del Piano F, Rouleau E, Tran-Dien A, Adam J, Lusque A, Jimenez M, Jacquet A, Garberis I, Andre F
Lien Pubmed
Résumé
The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized to either durvalumab (10 mg kg every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00-1.96; P = 0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54-1.29; P = 0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n = 82; HR: 0.54, 95% CI: 0.30-0.97, P = 0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12-1.13) for patients with PD-L1 TNBC (n = 32) and 0.49 (95% CI: 0.18-1.34) for those with PD-L1 TNBC (n = 29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05-0.71; log-rank test, P = 0.0059) in patients with CD274 gain/amplification (n = 23) and 1.12 (95% CI: 0.42-2.99; log-rank test, P = 0.8139) in patients with CD274 normal/loss (n = 32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.
Référence
Nat Med. 2021 Jan 18;:
