医学
曲妥珠单抗
乳腺癌
肿瘤科
内科学
表阿霉素
临床终点
多西紫杉醇
新辅助治疗
临床试验
癌症
作者
Xavier Pivot,Манихас Алексей Георгиевич,V. A. Shamrai,Giorgi Dzagnidze,Hwoei Fen,Viriya Kaewkangsadan,Fausto Petrelli,Cristian Villanueva,Липатов Олег Николаевич,Jocelyn Hii,Jamie Kim,Sumita Pradhan,Litha Jaison,Peggy Feyaerts,Leonard Kaufman,Marie-Paule Derde,Ghislain M. C. Bonamy,Filip Deforce,David Cox
出处
期刊:JAMA Oncology
[American Medical Association]
日期:2022-05-01
卷期号:8 (5): 698-698
被引量:7
标识
DOI:10.1001/jamaoncol.2021.8171
摘要
Importance
The drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab. Objective
To compare the efficacy of HD201 with referent trastuzumab. Design, Setting, and Participants
This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up. Interventions
Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab. Main Outcome and Measures
The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity. Results
A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at −3.8% (95% CI, −12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively. Conclusions and Relevance
The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile. Trial Registration
ClinicalTrials.gov Identifier:NCT03013504