Discussion
tumor, UTUC, renal pelvic or ureteral tumors, interstitial lung disease, bladder cancer, bladder urothelial carcinoma, deaths, TRAEs
NON-SMALL CELL LUNG CANCER, TUMOR, RECURRENCE, INTERSTITIAL LUNG DISEASE, BLADDER CANCER, INTERSTITIAL LUNG DISEASE
This report is the first to describe the efficacy and safety of adjuvant nivolumab in Japanese patients with MIUC enrolled in CheckMate 274, a large phase 3 trial that enrolled 709 patients across 29 countries, including 49 patients from Japan. In all randomized Japanese patients, the median DFS in the nivolumab and placebo groups was 29.67 and 9.72 months, respectively (HR 0.77, 95% CI 0.35–1.69). Despite the bias in patient background, these values are similar to the corresponding values in the ITT population reported previously (20.8 and 10.8 months, respectively; HR 0.70, 98.22% CI 0.55–0.90) (N+ is a risk factor for the recurrence of bladder cancer and UTUC (Among Japanese patients with tumor PD-L1 expression level of 1% or more, we found no clear difference in DFS between the nivolumab and placebo groups (median 29.67 and 25.95 months, HR 1.10, 95% CI 0.31–3.92) (A subgroup analysis of the overall population revealed the possibility of a larger effect size in patients with bladder urothelial carcinoma than in those with renal pelvic or ureteral tumors (CheckMate 274 also documented the safety of nivolumab in patients with MIUC. Of note, the analysis of Japanese patients identified no new safety signals for nivolumab, and the TRAEs were generally controllable by early diagnosis and appropriate therapies. Furthermore, there were no deaths related to the study drug among Japanese patients. In the nivolumab groups, TRAEs occurred in 77.5 and 59.3% of patients in the overall and Japanese populations, respectively, with Grade 3 or higher TRAEs in 17.9 and 25.9% of patients, respectively, and TRAEs leading to treatment discontinuation in 12.8 and 14.8% of patients, respectively (Two Japanese patients developed interstitial lung disease (one was considered related to the study drug). Both AEs were controlled and resolved after delaying or discontinuing nivolumab. The incidence of interstitial lung disease in this study was similar to that in prior Japanese studies of nivolumab monotherapy (Interstitial lung disease appears to be more common in real-world settings than in clinical trials based on data from post-marketing surveillance of nivolumab-treated patients with non-small cell lung cancer (We should acknowledge that the number of Japanese patients was small, which influenced the numerical frequencies of AEs. Therefore, we should be cautious when comparing the frequencies of AEs between Japanese patients and the overall study population.No meaningful changes in the EORTC QLQ-C30 scores were observed during treatment in either the Japanese population or the overall population. These results suggest that adjuvant nivolumab is unlikely to affect QOL.