A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data

Abstract

Background In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. Methods This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). Results Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression ( n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). Conclusion Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. Trial registration UMIN000033312 Electronic supplementary material The online version of this article (10.1007/s10147-020-01692-z) contains supplementary material, which is available to authorized users.

Tryptophan 2,3‐dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma

“…In this study, the median progression‐free survival (PFS) was 7.2 (95% confidence interval [CI]: 5.1‐14.3) months, and the median overall survival (OS) after ICI therapy was 22.9 (95% CI: 16.3‐NA) months. The 1‐year OS rate (n = 27) was 80.4% (95% CI: 63.2‐90.2), which was similar to that obtained in a Japanese multi‐institutional study 20 . In the Kaplan‐Meier analysis of PFS according to ICI treatment, the TDO expression level 3‐4 group had significantly poorer prognoses (median PFS, 4.9 months; 95% CI: 1.4‐5.4) than the TDO expression level 1‐2 group (median PFS, 14.3 months; 95% CI: 7.0‐NA; P < .001; Figure 5A).…”

Assessment of prognostic factors in previously treated Japanese patients with metastatic renal cell carcinoma who received nivolumab: An observational multi‑institute study

“…Recently, Hinata et al (21) reported the real-world prognostic outcomes of a wide range of Japanese patients with mRCC receiving nivolumab, and they were shown to be slightly poorer compared with those in the present study. The present study excluded patients who were diagnosed with non-clear cell RCC and/or received >3 molecular-targeted agents prior to the introduction of nivolumab in order to minimize the risk of bias induced by the heterogeneous characteristics of the included patients.…”

Outcome of immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines

“…Patients included in this analysis had a median duration of treatment (DOT) of 5. 15 Several reasons may account for these differences. First, our population is smaller, which may increase the risk of selection bias; second, 4.26% of our patients were treated beyond progression if a clinical benefit was documented; third, 65% of patients had a treatment escalation, i.e.…”