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

• Published in: Journal of clinical oncology Vol. 39; no. 13; pp. 1448 - 1457
• Main Authors: Piccart, Martine, Procter, Marion, Fumagalli, Debora, de Azambuja, Evandro, Clark, Emma, Ewer, Michael S, Restuccia, Eleonora, Jerusalem, Guy, Dent, Susan, Reaby, Linda, Bonnefoi, Hervé, Krop, Ian, Liu, Tsang-Wu, Pieńkowski, Tadeusz, Toi, Masakazu, Wilcken, Nicholas, Andersson, Michael, Im, Young-Hyuck, Tseng, Ling Ming, Lueck, Hans-Joachim, Colleoni, Marco, Monturus, Estefania, Sicoe, Mihaela, Guillaume, Sébastien, Bines, José, Gelber, Richard D, Viale, Giuseppe, Thomssen, Christoph
• Format: Journal Article Web Resource
• Language: English
• Published: United States 01-05-2021
• Subjects: Human health sciences; Oncologie; Oncology; Sciences de la santé humaine
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.20.01204

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],
= .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.
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.
This interim OS analysis comparing pertuzumab versus placebo did not reach the
= .0012 level required for statistical significance (
= .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.
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.