First-Line Treatment of HER2-Positive MBC

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The combination of trastuzumab, pertuzumab, and docetaxel was approved by the FDA in 2012 as a frontline therapy for patients with ER-negative, HER2-positive metastatic breast cancer, based on phase III findings from the CLEOPATRA trial. Following the approval, the combination became the standard of care at many community and academic institutions, suggests Dialecti Voudouris, MD.

In the CLEOPATRA trial, the median overall survival (OS) was 40.8 months with trastuzumab and docetaxel compared with 56.5 months with the addition of pertuzumab (HR = 0.68; P = .0002). The addition of pertuzumab extended progression-free survival by 6.3 months (median 18.7 vs 12.4 months; HR = 0.68; P <.0001).

Many questions exist regarding stopping chemotherapy and an optimal frontline therapy for patients with both HER2-positive and ER-positive disease, notes Sara Hurvitz, MD. In CLEOPATRA, treatment with docetaxel was continued for 6 cycles and then stopped. At this point, dual antibody therapy was continued until progression, which is what likely produced the impressive survival benefit, notes Hope S. Rugo, MD.

Adding an endocrine therapy to trastuzumab, pertuzumab, and docetaxel is an effective treatment for patients with ER-positive disease, Hurvitz states. The combination of trastuzumab with a hormonal therapy can result in much longer treatment durations, with some patients remaining on therapy for up to 10 years, Rugo suggests anecdotally.

In an 85-patient study, the median duration of treatment with fulvestrant and trastuzumab for HER2-positive patients was 772 days, compared with 360 days for HER2-negative patients who received trastuzumab alone (P = .059). The odds ratio for patients with HER2-positive breast cancer receiving a longer duration of treatment was 6.2 (P = .0249).