Abstract P2-16-07: Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with metastatic HER2-overexpressing metastatic breast cancer with cardiac biomarker data
Authors: Iyengar NM , Datko FM , D'Andrea G , Dickler MN , Goldfarb S , Theodoulou M , Lake D , Fornier MN , Modi S , Fasano J , Comen E , Gajria D , Moynahan ME , Traina TA , Patil S , Liu J , Jochelson M , Norton L , Hudis CA , Dang CT 
Published: August 2014

Abstract
Background: Pertuzumab (P), a monoclonal antibody that binds to extracellular domain II of HER2 distally from trastuzumab (H), disrupts HER2 dimerization and signaling. Dual anti-HER2 therapy with HP + docetaxel in HER2+ metastatic breast cancer (MBC) prolonged progression-free survival (PFS) in the placebo-controlled CLEOPATRA phase III trial. We report matured results of a phase II study to evaluate the efficacy and cardiac safety of weekly paclitaxel with HP (THP).
Methods: Patients (pts) with HER2+ MBC with 0-1 prior treatment (Rx) were eligible. Pts received weekly (w) paclitaxel (80mg/m2), q3w trastuzumab (loading dose 8mg/kg → 6mg/kg), and q3w pertuzumab (flat loading dose 840mg → flat dose 420mg). The primary endpoint was PFS at 6 months (mo). Secondary endpoints included response, safety (including cardiac events), and tolerability. Evaluable pts were those who had started study Rx and were able to be assessed at 6 mo for PFS. Safety and toxicity are reported for all enrolled patients. Left ventricular ejection fraction (LVEF) was monitored by echocardiogram (ECHO) every 3 mo. Cardiac enzymes including troponin I (TNI) and brain natriuretic peptide (BNP) were measured every other cycle x6. Cardiac events (CE) were defined as symptomatic LV systolic dysfunction (LVSD), non-LVSD cardiac death, or probable cardiac death.
Results: As of June 10th 2013, 63 pts were enrolled; 50 pts have reached the primary endpoint and were assessed at 6 mo for PFS. At 6 mo, 38/50 pts (76%) are progression-free (5 CR, 20 PR and 13 SD); 9 pts progressed; 3 pts were non-evaluable. The 6 mo PFS results for all patients will be updated. Of all enrolled pts (n = 63), median age was 52 years (range 26 to 72). A total of 28 pts (44%) previously received H in the adjuvant or metastatic setting, and 15 pts (24%) were being treated in the second-line metastatic setting. Safety and toxicity were assessed in all enrolled patients; G 3/4 toxicities were fatigue (3 pts, 5%), neutropenia (3 pts, 5%), peripheral neuropathy (2 pts, 3%), diarrhea (1 pt, 2%), hypomagnesium (1 pt, 2%), sepsis (1 pt, 2%), cellulitis (1 pt, 2%), and dry skin (1 pt, 2%). There were no febrile neutropenic (FN) events. Median LVEF was 64% at baseline (range 50% to 72%), 64% at 3mo (range 50% to 73%), 63% at 6mo (range 49% to 68%), 63% at 9 mo (range 47% to 68%), 64% at 12 mo (range 52% to 69%), 63% at 15 mo (range 55% to 69%), and 63% at 18 mo (range 56% to 68%). There were no CEs and no significant changes in TNI levels. Only 1 pt had a transient rise in BNP after cycle 1, but she did not have a CE.
Conclusions: Six-month PFS is 76% (95% CI 62-87%) in evaluable pts. Treatment is safe, with few grade 3/4 toxicities, no FN events, no CEs, and no significant or persistent elevation in TNI or BNP, respectively. THP is endorsed by the NCCN as a treatment option for pts with HER2+ MBC, as supported by this study. This study also suggests that intense serial LVEF monitoring may not be necessary with THP based on the cardiac safety results.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-07.