2018 ASCO Annual Meeting!
Session: The Arrival of Biosimilars
Type: Clinical Science Symposium
Time: Monday June 4, 9:45 AM to 11:15 AM
Location: Hall D1
Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial.
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 110)
Author(s): Aleksei Manikhas, Eduardo J. Pennella, Igor Bondarenko, Guzel Mukhametshina, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Sirshendu Ray, Cornelius F. Waller, Miguel Hernandez Bronchud, Jay Herson, Subramanian Loganathan, Abhijit Barve, Hope S. Rugo; City Clinical Oncology Dispensary, St. Petersburg, Russian Federation; Mylan Inc., Canonsburg, PA; Dnipropetrovsk Medical Academy, Dnipropetrovsk, Ukraine; Regional Clinical Oncological Center, Kazan, Russia; Cardinal Santos Medical Center, Manila, Philippines; Siriraj Hospital, Bangkok, Thailand; Sumy State University, Sumy Regional Clinical Oncology Center, Sumy, Ukraine; King Chulalongkorn Memorial Hospital, Chulalongkorn University,, Bangkok, Thailand; Curie Manavata Cancer Centre, Nasik, India; University of Freiburg Medical Center, Freiburg, Germany; Corachan Genesis-Care Clinic, Barcelona, Spain; Johns Hopkins Bloomberg School of Public Health, Chevy Chase, MD; Biocon Research Limited, Bangalore, India; Mylan, Canonsburg, PA; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
Background: The Heritage trial is a multicenter, double-blind, randomized, parallel-group, phase 3 study (NCT02472964) evaluating efficacy and safety of trastuzumab-dkst (Ogivri), a trastuzumab biosimilar, vs trastuzumab, in combination with taxane as first-line therapy for patients with HER2+ metastatic breast cancer. The primary endpoint, overall response rate on combination therapy at week 24, was previously reported (Rugo et al, JAMA 2017). Methods: Eligible patients were randomized 1:1 to trastuzumab-dkst or trastuzumab, combined with taxane. After 24 weeks, patients with responding or stable disease received monotherapy as per randomization. Here, we describe secondary endpoints of safety and immunogenicity during monotherapy and cumulative through 48 weeks; progression-free survival (PFS) and event-based overall survival (OS) will be presented in the future. Results: 500 patients were randomized, 342 continued treatment after 24 weeks, and 214 continued through 48 weeks. Treatment-emergent adverse event (TEAE) rates during monotherapy were similar (trastuzumab-dkst, 54.7%; trastuzumab, 60.1%); most were low grade. Grade ≥3 TEAEs were more frequent with trastuzumab (11.7%) vs trastuzumab-dkst (6.7%); serious TEAE rates were similar (trastuzumab-dkst, 2.8%; trastuzumab, 2.5%). When assessed over 48 weeks of combination and monotherapy, cumulative rates of TEAEs of special interest were similar for pulmonary events, significant cardiac disorders, and infusion-related events (trastuzumab-dkst, 13.0%, 4.9%, and 9.3%; trastuzumab, 12.2%, 4.1%, and 8.1%, respectively). Immunogenicity and incidence of left ventricular ejection fraction < 50% ≥1 time postbaseline and ≥10% reduction at week 48 were similar between groups (trastuzumab-dkst, 3.9% and 3.6%; trastuzumab, 4.4% and 2.8%, respectively). No new safety signals were detected. At week 48, median PFS was 11.1 months in both groups and OS curves were similar. Conclusions: Maintenance monotherapy with FDA-approved trastuzumab-dkst after combination with taxane was well tolerated, with safety and efficacy profiles similar to originator trastuzumab. Clinical trial information: NCT02472964