Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update
Authors: Loibl Sibylle , Jassem Jacek , Sonnenblick Amir , Parlier Damien , Winer Eric , Bergh Jonas , Gelber Richard D. , Restuccia Eleonora , Im Young-Hyuck , Huang Chiun-Sheng , Dalenc Florence , Calvo Isabel , Procter Marion , Caballero Carmela , Clark Emma , Raimbault Alice , McConnell Robin , Monturus Estefania , de Azambuja Evandro , Gomez Henry L. , Bliss Judith , Viale Giuseppe , Bines Jose , Piccart Martine ,   on behalf of the APHINITY Steering Committee and Investigators, Aebi Stefan , Andersson Michael , Bergh Jonas , Bines José , Bliss Judith , Bonnefoi Hervé , Caballero Carmela , Cameron David , Cardoso Fatima , Clark Emma , de Azambuja Evandro , de Haas Sanne , Dent Susan , Fein Luis , Frank Elizabeth , Gelber Richard , Gnant Michael , Gomez Moreno Henry , Im Seock-Ah , Jackisch Christian , Janni Wolfgang , Jassem Jacek , Krop Ian , Kümmel Sherko , Liu Tsang-Wu , Loi Sherene , Loibl Sibylle , Masuda Norikazu , Nili Gam-Yal Einav , Nyawira Beatrice , Pascual Tomas , Piccart Martine , Pienkowski Tadeusz , Procter Marion , Restuccia Eleonora , Rodríguez-Lescure Álvaro , Suter Thomas , Thomssen Christoph , Tjan-Heijnen Vivianne , Tomasello Gianluca , Torres Ulloa Manuel Roberto , Twelves Chris , Viale Giuseppe , Walshe Janice , Wilcken Nicholas , Winer Eric 
Published: September 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in
JCO
or elsewhere, for which the primary end point has already been reported.

The APHINITY trial (ClinicalTrials.gov identifier:
NCT01358877
) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2–positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02];
P
= .078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1%
v
81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor–negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.