Real-World Study Confirms Safety and Efficacy of Trastuzumab Biosimilar CT-P6 in HER2-Positive Gastric Cancer
核心洞察
A prospective post-marketing surveillance study of 171 patients demonstrated that the trastuzumab biosimilar CT-P6 achieved an 82.4% disease control rate and 7.4 months progression-free survival in HER2 (搜索)-positive advanced gastric cancer (搜索).
The safety profile showed 88.3% of patients experienced adverse events of any grade, with 32.2% experiencing grade ≥3 events, consistent with clinical trial data and no new safety concerns identified.
Five prognostic factors were identified as significantly associated with shorter progression-free survival, including gastroesophageal junction location, three or more metastases, no prior gastrectomy, prior chemotherapy, and lack of platinum combination therapy.
A comprehensive post-marketing surveillance study in Japan has provided the first prospective real-world evidence supporting the safety and efficacy of the trastuzumab biosimilar CT-P6 (trastuzumab-pkrb, Herzuma) in patients with HER2 (搜索)-positive advanced gastric cancer (搜索). The study, involving 171 patients, demonstrated a disease control rate of 82.4% and progression-free survival of 7.4 months, with no new safety concerns identified.
Critical Need for Gastric Cancer-Specific Evidence
The study addresses a significant gap in clinical evidence for CT-P6 in gastric cancer (搜索). While the biosimilar was approved in the European Union, United States, and Japan in 2018 for all indications of the reference product Herceptin, this approval was based on extrapolation from clinical trial data in HER2 (搜索)-positive breast cancer (搜索). The Japanese Ministry of Health, Labour, and Welfare required this post-marketing surveillance study as a condition for approval, highlighting the need for gastric cancer-specific evidence.
Safety Profile Consistent with Clinical Trials
The safety analysis revealed that adverse events occurred in 151 patients (88.3%), with 55 patients (32.2%) experiencing grade 3 or higher adverse events. Infusion reactions, the most frequent adverse event specific to antibody therapies, occurred in 12.3% of patients, almost all during the first infusion. These reactions resolved within a day and did not lead to treatment discontinuation or recurrence upon continued therapy.
Frequently observed adverse events included hematological toxicity, gastrointestinal disorders, peripheral neuropathy, and hand-foot syndrome, which are likely attributable to concomitant chemotherapy combined with CT-P6. The incidence rates were notably lower than those reported in the ToGA trial of the originator trastuzumab (99% for all grades and 68% for grade ≥3).
Cardiac disorders occurred in four patients (2.3%), including two cases of heart failure (搜索) (1.2%) due to trastuzumab-specific cardiac dysfunction (搜索). Interstitial lung disease (搜索) (ILD) developed in four patients (2.3%), all of whom recovered after treatment discontinuation and corticosteroid therapy. All patients who developed ILD were older males with prior chest imaging abnormalities, aligning with reported risk factors for drug-induced ILD.
Efficacy Outcomes and Treatment Response
The tumor response analysis showed an objective response rate of 34.4% and a disease control rate of 82.4%. Three patients (2%) achieved complete response. The progression-free survival of 7.4 months aligned well with the range of 5.9-9.2 months reported in originator studies. Notably, 17.9% of patients continued CT-P6 combination chemotherapy for one year, and eight patients successfully underwent conversion surgery.
Prognostic Factors Identified
Multivariable Cox regression analysis identified five significant poor prognostic factors associated with shorter progression-free survival: gastroesophageal junction site, number of metastases ≥3, no gastrectomy, prior chemotherapy, and lack of platinum combination. These findings provide valuable insights for treatment selection in real-world clinical practice.
Treatment Patterns and Regimen Effectiveness
The study revealed important differences in efficacy across various treatment settings. First-line therapy for inoperable advanced gastric cancer (搜索) and recurrence after curative resection showed comparable efficacy. Patients receiving second- or later-line therapy had higher progression rates and shorter treatment durations. The combination of CT-P6 with fluoropyrimidine (搜索) alone showed a low response rate of 4.3%, which improved significantly with the addition of oxaliplatin (33.3%) and even more with cisplatin (59.1%).
Clinical Practice Implications
During the one-year observation period, 123 patients (73%) discontinued treatment, with 89 (53%) discontinuing due to disease progression and 16 patients (9.5%) due to adverse events. The conversion surgery rate of 8.2% among 98 patients with primary unresectable disease was unexpectedly high for a multi-institutional study, demonstrating the potential for CT-P6 therapy to enable surgical intervention in previously inoperable cases.
The study's findings support the use of CT-P6 as an effective treatment option for HER2 (搜索)-positive advanced gastric cancer (搜索), providing clinicians with confidence in prescribing this biosimilar based on robust real-world evidence. The identification of prognostic factors also offers valuable guidance for patient selection and treatment planning in clinical practice.