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

A Correction to this article was published on 15 March 2023

This article has been updated


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.

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Fig. 1: Median progression free survival in patients treated with alpelisib + fulvestrant.

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All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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This work was supported by Novartis Pharma Sas. Novartis grants have been dedicated to the research purposes detailed below: Principal investigator & local sub-investigator time. Abstract & publication fees. Clinical Research Assistant time Database/Datamanager time. Statistical analysis. Preliminary data have been published as an abstract and a poster at the 2021 ASCO Annual Meeting (abstract number: 1064).

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Authors and Affiliations



Conceptualization: DBR, AG, FCB, FL. Methodology: DBR, AG, FCB, FL. Software: DBR, BR. Validation: DBR, AB, TDLMR, CB, SA, CB, MAB, ID, ZT, ER, JG, MS, BR, JG, HS, SD, MB, PC, AG, DL, JYP, FCB, FL. Formal analysis: BR. Resources: DBR, AB, TDLMR, CB, SA, CB, MAB, ID, ZT, ER, JG, MS, BR, JG, HS, SD, MB, PC, AG, DL, JYP, FCB, FL. Data Curation: DBR, BR, FCB, FL. Investigation: DBR, BR, FCB, FL. Writing - Original Draft: DBR, AB, TDLMR, CB, SA, CB, MAB, ID, ZT, ER, JG, MS, BR, JG, HS, SD, MB, PC, AG, DL, JYP, FCB, FL. Writing - Review & Editing: DBR, AB, TDLMR, CB, SA, CB, MAB, ID, ZT, ER, JG, MS, BR, JG,HS, SD, MB, PC, AG, DL, JYP, FCB, FL. Visualization: DBR, BR, FCB, FL. Supervision: DBR, AG, FCB, FL. Project administration: DBR, FCB, FL. Funding acquisition: FL.

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Correspondence to D. Bello Roufai.

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Competing interests

Institut Curie, represented in this work by Dr Florence Lerebours, has been funded by Novartis. DBR: Travel accommodations expenses: Daiichi Sankyo; Lilly; GSK. AB, TDLMR, CB, SA, CB, MAB, ID, ZT, ER, JG, MS: no relationships to disclose. JG: Travel accommodations expenses: AstraZeneca; Esai. HS: Honoraria: Lilly; Pfizer; Tesaro. Consulting or advisory role: Lilly; Mundipharla; Mylan; Novartis; Pierre Fabre; Roche; Sandoz; Vifor Pharma. Travel accommodations expenses: AstraZeneca; Lilly; Mundipharma; Novartis; Pfizer; Roche. SD: Consulting or advisory role: AstraZeneca; Pierre Fabre. Research funding: AstraZeneca; Exact Sciences; Lilly; Novartis; Pfiizer; Puma Biotechnolohy; Roche/Genentech; Sanofi. Travel accommodations expenses: AstraZeneca; Pfizer; Roche. MB: Travel accommodations expenses: Pfizer. Paul Cottu: Honoraria: Lilly; NanoString Technologies; Novartis; Pfizer; Pierre Fabre; Roche. Consulting or Advisory role: Lilly; Pfizer; Roche/Genentech. Research funding: Novartis; Pfizer. Travel accommodations expenses: Novartis; Pfizer. AG: Research Funding: Abbvie; AstaZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Cascadian Therapeutics; Lilly; Merus; MSD; Nektar; Novartis; Roche; Roche/Genentech; Sanofi/Aventis; Seattle Genetics. Travel accommodations expenses: Novartis. DL: Consulting or Advisory role: MSD Travel accommodations expenses: Bristol-Myers Squibb. JYP: Consulting or Advisory role or travel accommodations expenses: Pfizer, Lilly MSD, Roche, Novartis, AstraZeneca, Pierre Fabre, Servier, Daiichi et Ipsen. FCB: Consulting or advisory role: Archer; Lilly; Novartis; Pfizer; Radius Health; Sanofi. Speakers’ bureau: AstraZeneca; Novartis; Pfizer; Roche. Research Funding: Menarini Silicon Biosystems; Novartis; Pfizer; ProLynx; Roche; Servier. Patents, royalties, other intellectual property: ctDNA detection techniques. Travel accommodations expenses: Chugai Pharma; Novartis; Pfizer. FL: Travel accommodations expenses: Lilly; Novartis; Pfizer; Pierre Fabre; Roche.

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Bello Roufai, D., Gonçalves, A., De La Motte Rouge, T. et al. Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. Oncogene (2023).

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