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Clinical Trial
. 2025 Aug;25(6):554-559.e1.
doi: 10.1016/j.clbc.2025.04.016. Epub 2025 May 3.

Long-Term Safety and Efficacy of the Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-Positive Early Breast Cancer in PHranceSCa, a Randomized, Open-Label Phase II Study

Joyce O'Shaughnessy  1 , Susana Sousa  2 , Josefina Cruz  3 , Dame Lesley Fallowfield  4 , Päivi Auvinen  5 , Catarina Pulido  6 , Ana Cvetanovic  7 , Sharon Wilks  8 , Leonor Ribeiro  9 , Mauricio Burotto  10 , Thomas Boulet  11 , Valentine Revelant  11 , Nathalie Theron  11 , Peter Trask  12 , Laurentia Wahyudi  11 , Zuzana Kirchmayer Machackova  11 , Ljiljana Stamatovic  13
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Free article
Clinical Trial

Long-Term Safety and Efficacy of the Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-Positive Early Breast Cancer in PHranceSCa, a Randomized, Open-Label Phase II Study

Joyce O'Shaughnessy et al. Clin Breast Cancer. 2025 Aug.
Free article

Abstract

Background: We assessed long-term safety, efficacy, and health-related quality of life during the continuation phase after 3 years' follow-up in PHranceSCa (NCT03674112).

Patients and methods: This was a randomized, open-label, international, multicenter, crossover, Phase II study in adjuvant HER2-positive early breast cancer. One hundred fifty nine patients received 3 cycles of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC), then 3 of intravenous pertuzumab and trastuzumab (P + H IV), or vice versa. Postcrossover, patients continued preferred treatment (≤ 18 cycles total).

Results: Most adverse events, including all cardiac events (n = 2) and anaphylaxis/hypersensitivity (n = 3) were grade 1/2. None were grade 4/5. Grade 1/2 local injection-site reactions occurred in 13 patients (9.4%) receiving PH FDC SC. Other events occurred at comparable rates between arms. The overall event-free rate for invasive disease-free survival was 94.17% (95% confidence interval, 90.47-97.87) at 3 years; overall survival was 98.71% (96.92-100). Meaningful changes from baseline in health-related quality of life included improvements in role and social functioning, and reductions in financial difficulty.

Conclusion: PH FDC SC was well tolerated, with safety consistent with that of P + H IV (except local injection-site reactions) and no grade ≥ 3 anaphylaxis/hypersensitivity or new safety signals in the continuation period. Immature efficacy data showed high event-free rates, consistent with the known clinical benefit of pertuzumab and trastuzumab (although follow-up was relatively short at 3 years). PHranceSCa adds to the totality of evidence reinforcing the long-term clinical benefit and safety of pertuzumab and trastuzumab.

Keywords: Adjuvant therapy; Adverse events; Health-related quality of life; Invasive disease-free survival; Overall survival.

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Conflict of interest statement

Disclosures All authors received research support in the form of third-party medical writing assistance for this manuscript, provided by F. Hoffmann-La Roche Ltd. Dr O’Shaughnessy reported receiving honoraria for consulting and/or advisory boards from AbbVie, Inc., Agendia, Aptitude Health, AstraZeneca, Carrick Therapeutics, Daiichi Sankyo, Eisai, Fishawack Health, G1 Therapeutics, GlaxoSmithKline, Genentech, Inc., Gilead Sciences, Immunomedics, Eli Lilly, Loxo Oncology, Merck, Novartis, Ontada, Pfizer, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Roche, Samsung Bioepis, Sanofi, Seagen, and Stemline Therapeutics. Dr Cruz reported receiving speaker honoraria from GlaxoSmithKline, AstraZeneca, Roche, Novartis, Pharmamar, Eisai, Eli Lilly, Daiichi Sankyo, Gilead, Seagen, MSD, Pierre Fabre, and Pfizer; being in a consultant/advisory role for AstraZeneca, Roche, Novartis, Pharmamar, Eisai, Eli Lilly, Deciphera, GlaxoSmithKline, Daiichi Sankyo, Gilead, Seagen, and Pfizer; and travel expenses from Novartis, Gilead, Pharmamar, and Daiichi Sankyo. Dr Fallowfield reported receiving honoraria from AstraZeneca, BeiGene, Eisai, Medscape, Pfizer, Veracyte, Exact Sciences, and Novartis; consultancy/advisory roles for AstraZeneca, Eli Lilly, and Roche; and research funding from AstraZeneca, Eli Lilly, and Exact Sciences. Dr Pulido reported receiving speaker and/or advisory board honoraria from Gilead, AstraZeneca, Daiichi Sankyo, Leo, Novartis, and Servier; and travel expenses from Lilly. Dr Wilks reported being a speaker for Ideology. Dr Burotto reported being a consultant for AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Merck, Novartis, and Roche. Mr. Boulet reported being employed by Parexel GmbH who is contracted by F. Hoffmann-La Roche Ltd for statistical services in the conduct of the study. Dr Revelant, Dr Theron, Dr Wahyudi, and Dr Kirchmayer Machackova reported being employed by F. Hoffmann-La Roche Ltd and holding stocks and shares in F. Hoffmann-La Roche Ltd. Dr Trask reported being employed by Genentech, Inc. and holding stocks and shares in F. Hoffmann-La Roche Ltd. Dr Sousa, Dr Auvinen, Dr Cvetanovic, Dr Ribeiro, and Dr Stamatovic reported no further conflicts of interest to disclose.

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