by Hans Wildiers, Thomas Meyskens, Sandrine Marréaud,
Lissandra Dal Lago, Peter Vuylsteke, Giuseppe Curigliano, Simon Waters, Barbara
Brouwers, Bart Meulemans, Berta Sousa, Coralie Poncet, Etienne Brain
The Breast: Published: May 19, 2022
Introduction
Older patients are at higher risk of chemotherapy-induced
toxicity, raising interest in less toxic anti-HER2 regimens for older persons
with HER2-positive (HER2+) metastatic breast cancer (MBC).
Patients and methods
This phase II study randomized (1:1) patients with HER2+
MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral
cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP
alone. T-DM1 was offered in case of progression.
Results
In total, 39 and 41 patients were randomized to TP and TPM
arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95%
CI 8.2–32.4) and 28.7% (95% CI 15.8–43.0), respectively. A total of 49 (61.3%)
patients died of whom 37 (75.5%) from disease progression; number of deaths per
arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant
difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5
months, p 0.25). Among the 40 patients who have started T-DM1 after disease
progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95%
CI: 27.7–58.5) and grade 3 or higher AE occurred in 18 pts (45%).
Conclusions
Metronomic chemotherapy-based dual blockade (TPM), followed
by T-DM1 after progression, provides an active and relatively well tolerated
treatment option in an older/frail HER2+ MBC population, with a median survival
of over 3 years. Nevertheless, the majority of this older/frail population died
from breast cancer, highlighting the need for well tolerated and efficacious
treatments in these patients.
