Phase II study of weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer (MBC): Updated progression-free survival with overall survival result

Background: We previously reported results of the phase II breast cancer (BC) trial of weekly paclitaxel (T), trastuzumab (H) and pertuzumab (P) with its primary endpoint of 6-month (mo) progression-free survival (PFS) of 86% (95% CI, 75% to 92%) in patients (pts) with HER2+ metastatic (M) BC treated in first-and second-line settings. At a median (med) follow-up (FU) of 21 mo, med PFS was 19.5 mo overall. Updated PFS and OS analysis from this fully accrued study is presented here. Methods: Pts with HER2+ MBC with 0-1 prior treatment (Rx) were eligible. Rx was weekly (w) T (80mg/m2), q3w H (loading dose 8mg/kg →6mg/kg) and q3w P (loading dose 840mg →420mg), all given intravenously. Primary endpoint was 6 mo-PFS. Secondary endpoints included 6-mo and median OS. Evaluable pts received at least one full dose of Rx. Results: From January 2011 to December 2013, 69 pts were enrolled: 51 (74%) and 18 (26%) treated in first-and secondline metastatic settings, respectively. 67 were evaluable for efficacy. As of 12-01-14, 26/67 pts (39%) remain progression-free (6 CR, 13 PR and 7 SD); 34 pts have progressed and there are 51 survivors. At a med FU of 23 mo (range, 3-40 mo), 6mo PFS was 85% (95% CI, 74%-92%). Med PFS was 21.4 mo (95% CI, 13.8-NR) overall and 26.1 mo (95% CI, 17.0-NR) and 16.4 mo (95% CI, 8.5-NR) for pts with 0-1 prior Rx, respectively. 6-mo OS was 98% (95% CI, 90%-100%) and med OS was 37.5 mo (95% CI 31NR). Median duration of ChemoRx was 30 weeks. Rx was well-tolerated; there were no febrile neutropenia and no symptomatic left ventricular systolic dysfunction. Conclusions: Updated analysis demonstrates that weekly paclitaxel, when added to H and P, is associated with prolonged PFS and OS and a favourable toxicity profile and should be considered as a therapeutic option in this patient population.