TY - JOUR
T1 - Durvalumab compared to maintenance chemotherapy in metastatic breast cancer
T2 - the randomized phase II SAFIR02-BREAST IMMUNO trial
AU - Bachelot, Thomas
AU - Filleron, Thomas
AU - Bieche, Ivan
AU - Arnedos, Monica
AU - Campone, Mario
AU - Dalenc, Florence
AU - Coussy, Florence
AU - Sablin, Marie Paule
AU - Debled, Marc
AU - Lefeuvre-Plesse, Claudia
AU - Goncalves, Anthony
AU - Reynier, Marie Ange Mouret
AU - Jacot, William
AU - You, Benoit
AU - Barthelemy, Philippe
AU - Verret, Benjamin
AU - Isambert, Nicolas
AU - Tchiknavorian, Xavier
AU - Levy, Christelle
AU - Thery, Jean Christophe
AU - L’Haridon, Tifenn
AU - Ferrero, Jean Marc
AU - Mege, Alice
AU - Del Piano, Francesco
AU - Rouleau, Etienne
AU - Tran-Dien, Alicia
AU - Adam, Julien
AU - Lusque, Amelie
AU - Jimenez, Marta
AU - Jacquet, Alexandra
AU - Garberis, Ingrid
AU - Andre, Fabrice
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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−1 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.
AB - 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−1 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.
UR - http://www.scopus.com/inward/record.url?scp=85100070927&partnerID=8YFLogxK
U2 - 10.1038/s41591-020-01189-2
DO - 10.1038/s41591-020-01189-2
M3 - Article
C2 - 33462450
AN - SCOPUS:85100070927
SN - 1078-8956
VL - 27
SP - 250
EP - 255
JO - Nature Medicine
JF - Nature Medicine
IS - 2
ER -