The Effectiveness and Safety Profile of Nivolumab-Plus-Ipilimumab in Previously Untreated Japanese Patients With Advanced or Metastatic Renal Cell Carcinoma (J-ENCORE Study)

Abstract

Objectives: Combination therapy of nivolumab-plus-ipilimumab has been approved for advanced or metastatic renal cell carcinoma in Japan, but large-scale clinical data targeting Japanese patients is limited. To evaluate the early outcomes and factors related to early progression and response.

Methods: J-ENCORE is an ongoing multicenter, prospective, observational study of the effectiveness and safety of nivolumab-plus-ipilimumab for patients in Japan with advanced or metastatic renal cell carcinoma. The objective response rate, duration of response, progression-free survival, overall survival, incidence of adverse events, and factors related to early progression within 3 months, and response were assessed.

Results: We included 274 patients (median age: 68 years, 24.8% aged ≥ 75 years, 78.8% male). The median follow-up was 23.4 months. The objective response rate was 36.8%. Among responders, 63.3% had progression-free survival > 12 months. The median progression-free survival was 9.9 months; the 12-month overall survival was 76.3%. Of the patients, 77.0% experienced treatment-related adverse events, 42.3% experienced grade 3-4 events, and 1.1% experienced treatment-related death. Early progression was associated with female sex, poor risk status, liver metastasis, high baseline C-reactive protein levels, and high neutrophil-to-lymphocyte ratios. Responders were less likely to have bone metastases. Limitations include the observational nature of the study and a relatively short follow-up period.

Conclusions: This is the first prospective, real-world study to demonstrate the effectiveness and safety of nivolumab-plus-ipilimumab in Japan, with the results comparable to those of CheckMate 214. These findings support the use of nivolumab-plus-ipilimumab, although further studies with longer follow-up on nivolumab-plus-ipilimumab are needed.

Trail registration: ClinicalTrials.gov identifier: NCT04043975; University Hospital Medical Information Network-Clinical Trial Registration: UMIN000036772.

Keywords: Japan; ipilimumab; nivolumab; prospective study; renal cell carcinoma.

FIGURE 1

DOR (A), PFS (B), and OS (C) in all patients. CI, confidence interval; DOR, duration of response; NE, not estimated; NR, not reached; OS, overall survival; PFS, progression‐free survival.

FIGURE 2

OS in patients with and without early progression. CI, confidence interval; HR, hazard ratio; NE, not estimated; NR, not reached; OS, overall survival.