Martine Piccart1, Marion Procter2, Debora Fumagalli3, Evandro de Azambuja1, Emma Clark4, Michael S Ewer5, Eleonora Restuccia6, Guy Jerusalem7, Susan Dent8, Linda Reaby9,10, Hervé Bonnefoi11, Ian Krop12, Tsang-Wu Liu13, Tadeusz Pieńkowski14, Masakazu Toi15, Nicholas Wilcken16,17, Michael Andersson18,19, Young-Hyuck Im19, Ling Ming Tseng20, Hans-Joachim Lueck21, Marco Colleoni22, Estefania Monturus6, Mihaela Sicoe3, Sébastien Guillaume1, José Bines23, Richard D Gelber24, Giuseppe Viale25, Christoph Thomssen26. 1. Institut Jules Bordet and L'Université Libre de Bruxelles (ULB), Brussels, Belgium. 2. Frontier Science Scotland Ltd, Kincraig, Kingussie, United Kingdom. 3. Breast International Group (BIG), Brussels, Belgium. 4. Roche Products Limited, Welwyn Garden City, United Kingdom. 5. University of Texas, MD Anderson Cancer Center, Huston, TX. 6. Hoffmann-La Roche Ltd, Basel, Switzerland. 7. CHU Liege and Liege University, Liege, Belgium. 8. Duke Cancer Institute, Duke University, Durham, NC. 9. Inaugural Chair-Consumer Advisory Panel, Breast Cancer Trials Group, Newcastle, Australia. 10. Consumer Advisor to Breast Researchers, Garvan Institute of Research, Sydney, Australia. 11. Institute Bergonié, UNICANCER, University of Bordeaux, Bordeaux, France. 12. Dana-Farber Cancer Institute, Boston, MA. 13. National Health Research Institutes, Taipei, Taiwan. 14. Oncological Department, Postgraduate Medical Education Center, Warsaw, Poland. 15. Breast Cancer Unit, Kyoto University Hospital, Kyoto, Japan. 16. Director of Medical Oncology, Westmead Hospital, Sydney. 17. Associate Professor of Medicine, University of Sydney, Sydney, Australia. 18. Department of Oncology, Rigshospitalet, University Hospital, Copenhagen, Denmark. 19. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 20. Comprehensive Breast Health Center, Experimental Surgery, Department of Surgery, Taipei-Veterans General Hospital, Taipei, Taiwan. 21. Gynäkologisch-Onkologische Praxis Hannover, Hannover, Germany. 22. Division of Medical Senology, IEO, European Institute of Oncology, IRCCS, Milan, Italy. 23. Instituto Nacional de Câncer, Rio de Janeiro, Brazil. 24. Dana-Farber Cancer Institute, Harvard Medical School, Harvard TH Chan School of Public Health, Frontier Science Foundation, Boston, MA. 25. University of Milan, IEO, European Institute of Oncology, IRCCS, Milan, Italy. 26. Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
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.
RCT Entities:
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 humanepidermal 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.
Authors: Lifen Cao; Robert Shenk; Nickolas Stabellini; Megan E Miller; Christopher W Towe; Alberto J Montero Journal: Breast Cancer Res Treat Date: 2021-10-16 Impact factor: 4.872
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Authors: Alvaro Moreno-Aspitia; Eileen M Holmes; Christian Jackisch; Evandro de Azambuja; Frances Boyle; David W Hillman; Larissa Korde; Debora Fumagalli; Miguel A Izquierdo; Ann E McCullough; Antonio C Wolff; Kathleen I Pritchard; Michael Untch; Sébastien Guillaume; Michael S Ewer; Zhimin Shao; Sung Hoon Sim; Zeba Aziz; Georgia Demetriou; Ajay O Mehta; Michael Andersson; Masakazu Toi; Istvan Lang; Binghe Xu; Ian E Smith; Carlos H Barrios; Jose Baselga; Richard D Gelber; Martine Piccart-Gebhart Journal: Eur J Cancer Date: 2021-03-23 Impact factor: 9.162
Authors: Valentino Martelli; Maria Maddalena Latocca; Tommaso Ruelle; Marta Perachino; Luca Arecco; Kristi Beshiri; Maria Grazia Razeti; Marco Tagliamento; Maurizio Cosso; Piero Fregatti; Matteo Lambertini Journal: Breast Cancer (Dove Med Press) Date: 2021-05-24