Edith A Perez1, Carlos Barrios2, Wolfgang Eiermann3, Masakazu Toi4, Young-Hyuck Im5, Pierfranco Conte6,7, Miguel Martin8, Tadeusz Pienkowski9, Xavier B Pivot10, Howard A Burris11, Jennifer A Petersen12, Sanne De Haas13, Silke Hoersch13, Monika Patre13, Paul Anthony Ellis14. 1. Mayo Clinic, Jacksonville, Florida. 2. School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil. 3. Interdisciplinary Oncology Center, Munich, Germany. 4. Graduate School of Medicine, Kyoto University, Kyoto, Japan. 5. Samsung Medical Center, Seoul, Korea. 6. University of Padua, Padua, Italy. 7. Veneto Oncology Institute, Padua, Italy. 8. Hospital General Universitario Gregorio Marañon, Complutense University, CIBERONC, GEICAM, Madrid, Spain. 9. Postgraduate Medical Education Center, Warsaw, Poland. 10. Centre Paul Strauss, INSERM U1109, Strasbourg, France. 11. Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee. 12. Genentech, Inc, South San Francisco, California. 13. F. Hoffmann-La Roche, Ltd, Basel, Switzerland. 14. Guy's Hospital and Sarah Cannon Research Institute, London, United Kingdom.
Abstract
BACKGROUND: In the phase 3 MARIANNE trial, trastuzumab emtansine (T-DM1) with or without pertuzumab showed noninferior progression-free survival and better tolerability than trastuzumab plus a taxane (HT) for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. This article reports the final descriptive overall survival (OS) analysis, updated safety data, and additional patient-reported outcomes and biomarker analyses. METHODS: OS was assessed in 1095 patients with HER2-positive breast cancer and no prior therapy for advanced disease who had been randomized toHT, T-DM1 plus a placebo (hereafter T-DM1), or T-DM1 plus pertuzumab (T-DM1+pertuzumab). A post hoc exploratory landmark analysis of OS, baseline patient and disease characteristics, and tumor biomarkers in patients with and without an objective tumor response (OR) according to the Response Evaluation Criteria in Solid Tumors within 6.5 months of randomization was conducted. RESULTS: The median OS was similar across groups (50.9, 53.7, and 51.8 months for the HT, T-DM1, and T-DM1+pertuzumab groups, respectively). Among patients with an OR, the median OS was longer with T-DM1 (64.4 months) and T-DM1+pertuzumab (not reached) versus HT (56.3 months). No baseline characteristics or biomarkers were strongly associated with OR. The incidence of grade 3 or higher adverse events was greater with HT (55.8%) than T-DM1 (47.1%) or T-DM1+pertuzumab (48.6%). The median time to clinically meaningful deterioration (a 3-point or greater change) in neurotoxicity symptoms was shorter with HT (2.1 months) and T-DM1+pertuzumab (4.2 months) than T-DM1 (6.2 months). Fewer patients reported alopecia and diarrhea and were bothered by treatment side effects in the T-DM1 arm. CONCLUSIONS: These results support T-DM1 as a first-line treatment for patients with HER2-positive metastatic breast cancer who are deemed unsuitable for taxane-based therapy.
RCT Entities:
BACKGROUND: In the phase 3 MARIANNE trial, trastuzumab emtansine (T-DM1) with or without pertuzumab showed noninferior progression-free survival and better tolerability than trastuzumab plus a taxane (HT) for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. This article reports the final descriptive overall survival (OS) analysis, updated safety data, and additional patient-reported outcomes and biomarker analyses. METHODS: OS was assessed in 1095 patients with HER2-positive breast cancer and no prior therapy for advanced disease who had been randomized to HT, T-DM1 plus a placebo (hereafter T-DM1), or T-DM1 plus pertuzumab (T-DM1+pertuzumab). A post hoc exploratory landmark analysis of OS, baseline patient and disease characteristics, and tumor biomarkers in patients with and without an objective tumor response (OR) according to the Response Evaluation Criteria in Solid Tumors within 6.5 months of randomization was conducted. RESULTS: The median OS was similar across groups (50.9, 53.7, and 51.8 months for the HT, T-DM1, and T-DM1+pertuzumab groups, respectively). Among patients with an OR, the median OS was longer with T-DM1 (64.4 months) and T-DM1+pertuzumab (not reached) versus HT (56.3 months). No baseline characteristics or biomarkers were strongly associated with OR. The incidence of grade 3 or higher adverse events was greater with HT (55.8%) than T-DM1 (47.1%) or T-DM1+pertuzumab (48.6%). The median time to clinically meaningful deterioration (a 3-point or greater change) in neurotoxicity symptoms was shorter with HT (2.1 months) and T-DM1+pertuzumab (4.2 months) than T-DM1 (6.2 months). Fewer patients reported alopecia and diarrhea and were bothered by treatment side effects in the T-DM1 arm. CONCLUSIONS: These results support T-DM1 as a first-line treatment for patients with HER2-positive metastatic breast cancer who are deemed unsuitable for taxane-based therapy.
Authors: Maria Mitsogianni; Ioannis P Trontzas; Georgia Gomatou; Stephanie Ioannou; Nikolaos K Syrigos; Elias A Kotteas Journal: Oncol Lett Date: 2021-02-12 Impact factor: 2.967
Authors: Ian E Krop; Seock-Ah Im; Carlos Barrios; Hervé Bonnefoi; Julie Gralow; Masakazu Toi; Paul A Ellis; Luca Gianni; Sandra M Swain; Young-Hyuck Im; Michelino De Laurentiis; Zbigniew Nowecki; Chiun-Sheng Huang; Louis Fehrenbacher; Yoshinori Ito; Jigna Shah; Thomas Boulet; Haiying Liu; Harrison Macharia; Peter Trask; Chunyan Song; Eric P Winer; Nadia Harbeck Journal: J Clin Oncol Date: 2021-12-10 Impact factor: 50.717
Authors: Hussein F Aqbi; Cara Coleman; Melika Zarei; Saeed H Manjili; Laura Graham; Jennifer Koblinski; Chunquing Guo; Yibin Xie; Georgi Guruli; Harry D Bear; Michael O Idowu; Mehran Habibi; Xiang-Yang Wang; Masoud H Manjili Journal: Breast Cancer Res Date: 2020-10-28 Impact factor: 6.466