Switching gear and looking from a different angle in the treatment of HER2-positive disease

The results of the APHINITY trial were recently reported in the New England Journal of Medicine by von Minckwitz et al., wherein adjuvant pertuzumab was combined with trastuzumab plus chemotherapy in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (1). The addition of pertuzumab produced a 0.9% lower recurrence rate and death at 3 years (1). However, the absolute benefit was better in patients with lymph node metastases; in these patients, the rate of invasive disease-free survival (DFS) was 1.8% higher in the pertuzumab group than in the placebo group (1). Pertuzumab might have a position in adjuvant treatment for patients with multiple lymph node involvement or those willing to allow considerable adverse side effects in return for questionable benefit (1). Real-world clinical significance is perhaps subtler than the rigid numbers that determine statistical significance in clinical trials. The results for pertuzumab in the APHINITY trial were statistically significant with reference to the primary endpoint of invasive DFS (1). However, compared to results of pertuzumab treatment in the context of advanced breast cancer (CLEOPATRA) and the neoadjuvant setting (NeoSphere), the results of APHINITY were a clinical and scientific disappointment (1-3).