QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial.

BACKGROUND: This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS: Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS: Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS: QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION: Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study.

OBJECTIVE: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. METHODS: From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. RESULTS: The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. CONCLUSION: This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.