Phase II Study of Paclitaxel Given Once per Week Along With Trastuzumab and Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Abstract

Purpose The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients and Methods Patients with metastatic human epidermal growth factor receptor 2–positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m2 once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. Results From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusion Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy.

Incidence, Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

“…Adding pertuzumab, another HER2-directed humanized monoclonal antibody, to trastuzumab does not appear to increase these risks in recent clinical trials (35, 36). Thus, the results from repeated echocardiographic monitoring on clinical trials demonstrate that the incidence of LVEF decline in patients receiving modern trastuzumab-based regimens without concurrent anthracycline is low, especially in patients without a low baseline LVEF (20, 28, 37–41). These data, along with the high rate of reversibility for trastuzumab-induced cardiotoxicity, favor continued trastuzumab use even in the face of asymptomatic LVEF declines (25, 42, 43).…”

Impressive Long-term Response with Pertuzumab and Trastuzumab in HER2-positive Breast Cancer with Brain Metastasis

“…Recently, Dang et al demonstrated that paclitaxel given once per week with T and P is highly effective and welltolerated and could be an alternative to docetaxel-based combination therapy in first and second line setting (14).…”

A modern paradigm for treating HER2-positive advanced breast cancer: Dual HER2 blockade and antibody-drug conjugates

“…Так, в исследование NCT01276041, где анти-HER2-препараты применялись совместно с паклитакселом (80 мг/м 2 еже-недельно), было рекрутировано 69 больных, для 51 (74%) из которых это была первая линия лечения и для 18 (26%) вторая. Медиана ВБП составила 24,2 мес для первой ли-нии и 16,4 мес для второй линии терапии [23]. То есть схема с паклитакселом сопоставима по эффективности с терапией доцетакселом, при которой медиана ВБП со-ставила 18,7 мес [14].…”