Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
Combination of Olaparib, Durvalumab, and Fulvestrant in Patients with Advanced ER+/HER2- Breast Cancer and Selected Genomic Alterations: Results of the DOLAF Trial.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Guiu Séverine, Balmaña Judith, Lemercier Pablo, Follana Philippe, Gonçalves Anthony, Bigot Frédéric, Frenel Jean-Sébastien, Brain Etienne, Mailliez Audrey, Chakiba Brugere Camille, Curtit Elsa, Derbel Olfa, Dalenc Florence, Derquin Fanny, Duhoux François, Canon Jean-Luc, Pimentel Isabel, Chevalier Louise Marie, Buisson Adrien, Guyonneau Clara, Lemonnier Jérôme, Delaloge Suzette, Bachelot Thomas
Аннотация
PURPOSE: Previous data suggest synergy between PARP inhibition and immune checkpoint blockade in different genetic settings. The estrogen receptor (ER) pathway remains a key target in metastatic breast cancer regardless of genomic context. This study assesses the activity of the combination of PARP, ER, and PD-L1 inhibition among patients with metastatic breast cancer and relevant genomic alterations.
PATIENTS AND METHODS: In this multicenter, single-arm, phase II clinical trial, we used a Simon two-stage design to evaluate the activity and safety of a combination of durvalumab, olaparib, and fulvestrant as second or third line in patients with ER+/HER2- metastatic breast cancer. Patients with either somatic or germline mutations of a homologous recombination repair gene, a microsatellite instability status, or an endocrine resistance-related mutation were eligible. Primary endpoint was 24-week progression-free survival rate.
RESULTS: The 172 (100%) patients included received prior endocrine therapy for metastatic breast cancer and 86% received a CDK4/6 inhibitor, and 67 (39%) had a previously documented germline BRCA1/2 mutation (gBRCA1/2m). The 24-week progression-free survival rate was 66.7% [95% confidence interval (CI), 58.6-74.1] in the evaluable population and 76.3% (95% CI, 63.4-86.4) in gBRCA1/2m patients. The median progression-free survival was 9.3 months (95% CI, 7.5-12.7) and 12.6 months (95% CI, 8.2-16.7) in the intention-to-treat and gBRCA1/2m populations, respectively. The median overall survival was 30 months (95% CI, 26.6-not reached). Most common adverse events of any grade were nausea (59%) and asthenia (43%). No new toxicity warning was detected.
CONCLUSIONS: In patients with ER+/HER2- metastatic breast cancer and selected genomic alterations, this triplet combination was active and had an acceptable toxicity profile (NCT04053322).
PATIENTS AND METHODS: In this multicenter, single-arm, phase II clinical trial, we used a Simon two-stage design to evaluate the activity and safety of a combination of durvalumab, olaparib, and fulvestrant as second or third line in patients with ER+/HER2- metastatic breast cancer. Patients with either somatic or germline mutations of a homologous recombination repair gene, a microsatellite instability status, or an endocrine resistance-related mutation were eligible. Primary endpoint was 24-week progression-free survival rate.
RESULTS: The 172 (100%) patients included received prior endocrine therapy for metastatic breast cancer and 86% received a CDK4/6 inhibitor, and 67 (39%) had a previously documented germline BRCA1/2 mutation (gBRCA1/2m). The 24-week progression-free survival rate was 66.7% [95% confidence interval (CI), 58.6-74.1] in the evaluable population and 76.3% (95% CI, 63.4-86.4) in gBRCA1/2m patients. The median progression-free survival was 9.3 months (95% CI, 7.5-12.7) and 12.6 months (95% CI, 8.2-16.7) in the intention-to-treat and gBRCA1/2m populations, respectively. The median overall survival was 30 months (95% CI, 26.6-not reached). Most common adverse events of any grade were nausea (59%) and asthenia (43%). No new toxicity warning was detected.
CONCLUSIONS: In patients with ER+/HER2- metastatic breast cancer and selected genomic alterations, this triplet combination was active and had an acceptable toxicity profile (NCT04053322).