Efficacy of nivolumab versus molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma: Real‐world data from two Japanese institutions

Abstract

ObjectivesTo compare the efficacy of nivolumab with that of molecular‐targeted therapy as a second‐line therapy for metastatic renal cell carcinoma using real‐world data.MethodsWe retrospectively evaluated patients who received nivolumab or molecular‐targeted therapy after the failure of first‐line molecular‐targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression‐free survival and overall survival after the initiation of second‐line therapy were calculated using the Kaplan‐Meier method and compared using the log‐rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1.ResultsAmong 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular‐targeted therapy as second‐line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression‐free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular‐targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular‐targeted therapy (n = 14/41 [34%] vs n = 20/110 [18%], P = 0.0485).ConclusionsReal‐world data analysis suggests superior efficacy of nivolumab over molecular‐targeted therapy as second‐line therapy for metastatic renal cell carcinoma.

Clinical factors for tumor response, progression, and survival in nivolumab for advanced renal cell carcinoma in the SNiP‐RCC study

“…On the other hand, Ishihara et al. found that poor MSKCC (which include KPS < 70, high calcium, and low hemoglobin levels) and C‐reactive protein levels were independent factors for PFS and OS, in a Japanese population treated with nivolumab monotherapy or mTOR inhibitor for advanced RCC with prior therapy 18 . Additionally, clear cell histopathology was a prognostic factor for PFS.…”

Real‐world effectiveness of nivolumab and subsequent therapy in Japanese patients with metastatic renal cell carcinoma (POST‐NIVO study): 36‐month follow‐up results of a clinical chart review

“…17 The Japanese realworld data were more favorable than that of the overseas population, with a mOS of over 45.9 months and mPFS of 5.06-10.3 months. 9,11,12 However, these studies had some limitations in interpreting survival data including short follow-up durations (≤1 year), a small number of patients (≤100), and/or few sites (≤6). 9,11,12 Although this study included diverse realworld patients from 17 sites with a relatively long follow-up, the results of this study were comparable with those of pivotal trials 6,8 and other real-world studies.…”

“…9,11,12 However, these studies had some limitations in interpreting survival data including short follow-up durations (≤1 year), a small number of patients (≤100), and/or few sites (≤6). 9,11,12 Although this study included diverse realworld patients from 17 sites with a relatively long follow-up, the results of this study were comparable with those of pivotal trials 6,8 and other real-world studies. 9,11,17 The AFTER I-O study 18 retrospectively analyzed Japanese patients with mRCC who received molecular-targeted therapies after nivolumab and were enrolled in CheckMate 025 2 or CheckMate 214, 19 and reported a mOS from first-line treatment of 70.5 months.…”

“…In a previous Dutch study that retrospectively analyzed nivolumab real‐world data included patients with poor prognostic factors (third‐line, 16%; non‐clear cell RCC, 7%; brain metastases, 11%) and showed mOS and mPFS of 18.7 and 5.6 months, respectively 17 . The Japanese real‐world data were more favorable than that of the overseas population, with a mOS of over 45.9 months and mPFS of 5.06–10.3 months 9,11,12 . However, these studies had some limitations in interpreting survival data including short follow‐up durations (≤1 year), a small number of patients (≤100), and/or few sites (≤6) 9,11,12 .…”

“…[6][7][8] Longer mOS than the global population of CheckMate 025 has been reported in several Japanese studies evaluating the outcomes of nivolumab monotherapy for mRCC in real-world settings. [9][10][11][12] However, these studies provided limited data because of a short follow-up, a small number of patients, and/ or few sites. Therefore, it is important to examine the effectiveness and safety of nivolumab in a larger number of patients with mRCC under real-world conditions, with a longer follow-up.…”