The benefit of adjuvant pertuzumab and trastuzumab according to estrogen receptor and HER2 expression: a subanalysis of the APHINITY trial

BACKGROUND: Responses to anti-HER2 therapy can vary based on estrogen receptor expression and HER2 gene amplification. This study assessed the magnitude of benefit by adding pertuzumab to trastuzumab and chemotherapy by estrogen receptor and HER2 levels in the APHINITY trial. METHODS: APHINITY (ClinicalTrials.gov identifier NCT01358877; BIG 4-11) was a randomized, double-blind, phase 3 trial comparing pertuzumab with placebo added to adjuvant trastuzumab and chemotherapy in 4804 patients with HER2-positive early breast cancer. The primary endpoint of this exploratory analysis was invasive disease-free survival (IDFS). Subgroup analyses used Cox models across 4 groups defined by HER2 fluorescence in situ hybridization (FISH) ratio and estrogen receptor status, adjusted for treatment arm, chemotherapy regimen, and a combined variable of nodal status and protocol version. Tumors with a FISH ratio below 2 were excluded, leaving 4782 evaluable cases. The HER2 FISH ratio was classified as low (2 to