Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).

Abstract

606 Background: Pertuzumab is a monoclonal antibody which binds to extracellular domain II of HER2 distally from trastuzumab, disrupting HER2 dimerization and signaling. Pertuzumab improves progression-free survival (PFS) and overall survival when combined with docetaxel/trastuzumab. We report results of a phase II study to evaluate the efficacy and safety of pertuzumab, trastuzumab and weekly paclitaxel. Methods: Patients (pts) with HER2+ MBC with 0-1 prior treatment (Rx) were eligible. Rx is weekly (w) paclitaxel (80mg/m2), q3w trastuzumab (loading dose 8mg/kg → 6mg/kg), and q3w pertuzumab (flat loading dose 840mg → 420mg). The primary endpoint is PFS at 6 months (mo). Evaluable pts are those who started study Rx and are assessed at 6 mo for PFS, including pts who progressed prior to 6mo. Secondary endpoints include response, safety (including cardiac events), and tolerability. Left ventricular ejection fraction (LVEF) is monitored by echocardiogram every 3 mo. Cardiac events are defined as symptomatic LV systolic dysfunction (LVSD), non-LVSD cardiac death, or probable cardiac death. Results: As of 1-18-13, 53 pts are enrolled; 36 are evaluable at 6 mo. At 6 mo, 29/36 pts (81%) are progression-free (4 CR, 14 PR and 11 SD); 7 pts progressed. The 6 mo PFS results for all patients will be updated. Median LVEF is 64% at baseline (range 50-72%), 63% at 3 mo (range 50-73%), and 62% at 6 mo (range 49-69%). There are no cardiac events to date. Of the 36 pts, grade 3/4 toxicities include fatigue (3 pts, 8%), peripheral neuropathy (2 pts, 6%), sepsis (1pt, 3%), cellulitis (1pt, 3%), neutropenia (1pt, 3%), and skin ulceration (1pt, 3%). There are no grade 3 diarrhea or febrile neutropenic events in the evaluable pts to date. Conclusions: The preliminary 6-month PFS is 81% (95% CI 67-91%) in evaluable patients. The study is closing to accrual. Treatment is ongoing, with few grade 3/4 toxicities and no signal of increased cardiac toxicity to date. This phase II study demonstrates efficacy and safety for pertuzumab with trastuzumab and weekly paclitaxel in HER2+ MBC. Clinical trial information: NCT01276041.

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

“…This study confirms that dual HER-2 blockade is both effective and safe. Although there is some indication of benefit of weekly paclitaxel in combination with pertuzumab and trastuzumab [56], the merits of chemo-therapy companions other than docetaxel for dual HER-2 inhibition remain unclear. Ongoing trials investigating alternative chemotherapies may prove helpful in identifying chemotherapy partners, as well as providing further evidence for the benefits of this regimen in patients receiving prior chemotherapy and trastuzumab [56 -58].…”

Pertuzumab: A New Targeted Therapy for HER2-Positive Metastatic Breast Cancer

“…Finally, a phase II study presented at the 2012 SABCS explored the benefit of using pertuzumab with trastuzumab and weekly paclitaxel in patients with HER2-positive MBC with zero or one prior therapy for metastatic disease. 40 This study is still ongoing, but early data in 33 patients suggest that 76% of patients are progression free at 6 months. The final results of this study may help to determine if pertuzumab and trastuzumab have similar efficacy when combined with docetaxel or paclitaxel in firstline therapy for HER2-positive MBC.…”

“…Pertuzumab has been evaluated as a single agent and in combination with trastuzumab and/ or chemotherapy in patients with advanced HER2-positive breast cancer. [36][37][38][39][40] Details of these studies, including study design and dosing information, are listed in Table 2. Activity with pertuzumab is limited to patients with HER2-positive disease, as a phase II study that evaluated pertuzumab monotherapy in HER2-negative metastatic breast cancer showed limited efficacy.…”

“…The study enrolled 66 patients who completed a median of nine cycles. Prior treatment included an anthracycline 40 Datko, et al or taxane in 70% and 41% of patients, respectively. Overall, five patients (7.6%) achieved a CR and 11 patients (16.7%) achieved a PR, for an ORR of 24.3%.…”

“…Paclitaxel (NCCN category 2A recommendation) has been studied in combination with pertuzumab and trastuzumab in a small phase II clinical trial presented at the 2012 SABCS with results similar to the combination of docetaxel, pertuzumab, and trastuzumab. 40 Based on the available data, the combination of docetaxel, trastuzumab, and pertuzumab is the most appropriate first-line therapy for HER2-positive MBC. However, weekly paclitaxel could also be utilized in combination with pertuzumab and trastuzumab based on the differing toxicity profile of weekly paclitaxel compared with docetaxel.…”