Hope S Rugo1, Eduardo J Pennella2,3, Unmesh Gopalakrishnan4, Miguel Hernandez-Bronchud5, Jay Herson6, Hans Friedrich Koch7, Subramanian Loganathan8, Sarika Deodhar8, Ashwani Marwah8, Alexey Manikhas9, Igor Bondarenko10, Guzel Mukhametshina11, Gia Nemsadze12, Joseph D Parra13, Maria Luisa T Abesamis-Tiambeng14, Kakhaber Baramidze15, Charuwan Akewanlop16, Ihor Vynnychenko17, Virote Sriuranpong18, Gopichand Mamillapalli19, Sirshendu Roy20, Eduardo Patricio Yanez Ruiz21, Abhijit Barve2, Adolfo Fuentes-Alburo2, Cornelius F Waller22. 1. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu. 2. Viatris Inc, Canonsburg, PA, USA. 3. MaxCyte, Inc, Gaithersburg, MD, USA. 4. Viatris Inc, Bangalore, India. 5. GénesisCare Corachan, Barcelona, Spain. 6. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. 7. Viatris Inc, Hannover, Germany. 8. Biocon Research Limited, Bangalore, India. 9. City Clinical Oncology Dispensary, Saint Petersburg, Russia. 10. Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine. 11. Regional Clinical Oncological Center, Kazan, Russia. 12. Institute of Clinical Oncology, Tbilisi, Georgia. 13. St Luke's Medical Center, Quezon City, Philippines. 14. Cardinal Santos Medical Center, Manila, Philippines. 15. Golden Fleece 21 Century Health House Ltd, Tbilisi, Georgia. 16. Siriraj Hospital, Bangkok, Thailand. 17. Sumy State University, Sumy, Ukraine. 18. King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand. 19. City Cancer Center, Vijayawada, India. 20. Curie Manavata Cancer Centre, Nasik, India. 21. Universidad de la Frontera, Temuco, Chile. 22. Department of Haematology, Oncology and Stem Cell Transplantation, University Medical Centre Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Abstract
PURPOSE: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE. METHODS: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient. RESULTS: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in thetrastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up. CONCLUSION: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015.
RCT Entities:
PURPOSE: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE. METHODS: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient. RESULTS: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up. CONCLUSION: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015.
Entities:
Keywords:
Biosimilar; Metastatic breast cancer; Overall survival; Trastuzumab
Authors: D J Slamon; B Leyland-Jones; S Shak; H Fuchs; V Paton; A Bajamonde; T Fleming; W Eiermann; J Wolter; M Pegram; J Baselga; L Norton Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
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