Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up

Abstract

PURPOSE APHINITY, at 45 months median follow-up, showed that pertuzumab added to adjuvant trastuzumab and chemotherapy significantly improved invasive disease–free survival (IDFS) (hazard ratio 0.81 [95% CI, 0.66 to 1.00], P = .045) for patients with early human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC), specifically those with node-positive or hormone receptor (HR)–negative disease. We now report the preplanned second interim overall survival (OS) and descriptive updated IDFS analysis with 74 months median follow-up. METHODS After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab. RESULTS This interim OS analysis comparing pertuzumab versus placebo did not reach the P = .0012 level required for statistical significance ( P = .17, hazard ratio 0.85). Six-year OS were 95% versus 94% with 125 deaths (5.2%) versus 147 (6.1%), respectively. IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively. The node-positive cohort continues to derive clear IDFS benefit from pertuzumab (hazard ratio 0.72 [95% CI, 0.59 to 0.87]), 6-year IDFS being 88% and 83%, respectively. Benefit was not seen in the node-negative cohort. In a subset analysis, IDFS benefit from pertuzumab showed a hazard ratio of 0.73 (95% CI, 0.59 to 0.92) for HR-positive disease and a hazard ratio of 0.83 (95% CI, 0.63 to 1.10) for HR-negative disease. Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen. CONCLUSION This analysis confirms the IDFS benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early BC. Longer follow-up is needed to fully assess OS benefit.

Update Breast Cancer 2021 Part 3 – Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel

“…Consistent with the six-year follow-up data of the APHINITY study [54], in the case of a clinically (i.e. pre-therapeutically) nodal-positive patient, 56 % of panellists were in favour of blockade with trastuzumab + pertuzumab, while in the case of an initially nodal-negative patient, 70 % were in favour of administration of trastuzumab alone [54,55]. In the presence of residual invasive tumour (non-pCR), 90 % were in favour of the postneoadjuvant administration of trastuzumab-emtansine (T-DM1) in line with the data from the Katherine study [48].…”

“…With regard to patients with HER2-positive breast carcinoma who received neoadjuvant treatment, panellists were asked whether adjuvant HER2-targeted therapy should be continued after achieving a pCR (Supplementary Table S1, questions [74][75]. Consistent with the six-year follow-up data of the APHINITY study [54], in the case of a clinically (i.e. pre-therapeutically) nodal-positive patient, 56 % of panellists were in favour of blockade with trastuzumab + pertuzumab, while in the case of an initially nodal-negative patient, 70 % were in favour of administration of trastuzumab alone [54,55].…”

“…At present, the consensus is that node-negative breast cancer patients should not also be treated with the antibody therapy combination trastuzumab + pertuzumab. The APHINITY trial involving 4805 patients showed no benefit for patients with node-negative breast cancer after a median follow-up of 74 months [54]. The analysis to date considers inva-sive recurrences and metastases, as data on overall survival is currently lacking.…”

“…The analysis to date considers inva-sive recurrences and metastases, as data on overall survival is currently lacking. A subgroup analysis of patients with 1-3 affected lymph nodes (38 % of the total population) and patients with more than 4 affected axillary lymph nodes (25 % of the total population) is, as yet, not available [54].…”

Comparing the Gonadotoxicity of Multiple Breast Cancer Regimens: Important Understanding for Managing Breast Cancer in Pre-Menopausal Women

“…Pertuzumab is another intravenous anti-HER2 antibody, used with trastuzumab also in early settings as both neoadjuvant and adjuvant therapy. 68,69 There is a lack of evidence about its possible effects on fertility. 14 Neratinib is an anti-HER2 drug taken orally and used in an adjuvant setting after trastuzumab-based therapy.…”