Safety evaluation of fixed-dose nivolumab in patients with gastric cancer.

Background and Aims: This study aimed to examine the safety of fixed-dose nivolumab. Methods: We retrospectively reviewed the medical records of 113 Japanese patients with gastric cancer who were previously treated with cytotoxic chemotherapy and initiated nivolumab. The endpoints were the incidence of Grade 2 or higher immune-related adverse events (irAEs) in the conventional dose (3 mg/kg) and fixed-dose groups (240 mg). Results: The incidence rates of irAEs in the conventional-dose and fixed-dose groups were 29.9% and 19.4%, respectively, and the rates of Grade 2 or higher irAEs were 23.3% and 19.4%, respectively, with no significant difference between the two groups, suggesting that nivolumab at 240 mg is as safe as the 3 mg/kg dose. Conclusion: This is the first report on the safety of nivolumab at 240 mg in Japanese patients.

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Immune-related adverse events (irAEs) are associated with the efficacy of immune-checkpoint inhibitors in patients with melanoma and non-small cell lung cancer. We therefore evaluated the relationship between irAEs and nivolumab efficacy against metastatic renal cell carcinoma. PATIENTS AND METHODS: The medical records of 53 consecutive patients were reviewed and analyzed. RESULTS: Median overall survival was significantly better in patients who showed irAEs at any time compared to patients without irAEs (p=0.013). We identified irAEs in 24 of 53 patients (45.3%), including four patients (7.5%) with grade 3 events. Multivariate analysis also revealed that risk factors for the onset of irAEs were positively associated with a platelet-to-lymphocyte ratio <156 before nivolumab treatment (p=0.006). CONCLUSION: Development of irAEs was associated with survival outcomes of nivolumab treated patients with metastatic renal cell carcinoma.

Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma.

PURPOSE: Immune-related adverse events (irAEs) have been associated with the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with urothelial cancer. We therefore evaluated the relationship between irAEs and pembrolizumab efficacy in urothelial cancer patients. METHODS: Patients with urothelial cancer who were treated with pembrolizumab in a second-line setting or later between January 2018 and December 2018 were identified by reviewing their medical records from the Cancer Institute Hospital, Japanese Foundation for Cancer Research. Data were updated as of December 31, 2018. Kaplan-Meier curves for overall survival (OS) and time to treatment failure (TTF) according to irAE grade were evaluated using the log-rank test. Risk factors for exacerbation of irAEs were also evaluated with multivariate analysis. RESULTS: In this retrospective study, 43 patients received pembrolizumab. We identified irAEs in 22 of the 43 patients (51.2%), including 11 patients (25.6%) with grade 2 or 3 events. In patients with irAE grade 0 or 1, median TTF was 127 days, and median OS was 160 days according to the Kaplan-Meier method. On the other hand, in patients with irAE grade ≥2, median TTF and OS were not reached. Multivariate analysis also revealed that risk factors for exacerbation of irAEs (to grade ≥2) were positively associated with lymphocyte count at baseline (>2,000/µL) before pembrolizumab treatment (p = 0.021). CONCLUSIONS: Development of irAEs was associated with survival outcome of pembrolizumab treatment in patients with advanced urothelial cancer.