Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program

D. Bello Roufai, A. Gonçalves, T. De La Motte Rouge, S. Akla, C. Blonz, J. Grenier, J. Gligorov, M. Saghatchian, C. Bailleux, H. Simon, I. Desmoulins, Z. Tharin, E. Renaud, M. Bertho, M. A. Benderra, S. Delaloge, L. Robert, P. Cottu, J. Y. Pierga, D. LoiratA. Bertucci, B. Renouf, F. C. Bidard, F. Lerebours

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    Abstract

    SOLAR-1 and BYLieve trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP) opened to PIK3CA-mutant HR+/HER2- ABC patients treated with alpelisib and fulvestrant. Primary endpoint was PFS by local investigators using RECIST1.1. Eleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1–16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95% CI: 4.7–6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95% CI: 37.8–52.8). In multivariable analysis, characteristics significantly associated with a shorter PFS were age < 60 years (HR = 1.5, 95% CI = 1.1–2.1), >5 lines of prior treatments (HR = 1.4, 95% CI = 1.0–2.0) and the C420R PI3KCA mutation (HR = 4.1, 95% CI = 1.3–13.6). N = 91 (39.1%) patients discontinued alpelisib due to adverse events. To our knowledge, this is the largest real-life assessment of alpelisib efficacy. Despite heavy pre-treatments, patients derived a clinically relevant benefit from alpelisib and fulvestrant.

    Original languageEnglish
    Pages (from-to)1951-1956
    Number of pages6
    JournalOncogene
    Volume42
    Issue number23
    DOIs
    Publication statusPublished - 6 Jun 2023

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