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.

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.