Real-world efficacy and safety of nivolumab plus ipilimumab in untreated metastatic renal cell carcinoma, and the impact of previous nephrectomy on clinical outcome: Japanese multi-institutional retrospective study

Background In metastatic renal-cell carcinoma (mRCC), recent clinical trials have shown efficacy of first-line combination therapy, as evidenced by better clinical outcome over target therapy. However, there are insufficient real-world evidences in mRCC patients in Japan. Methods We performed a multicenter retrospective study of 72 mRCC patients who received nivolumab plus ipilimumab as first-line treatment between September 2018 and July 2021. Patient’s characteristics, clinical outcomes and safety were retrospectively reviewed. We analyzed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients treated with combination therapy. Results Of all patients, the median age was 70 years (range, 36–86) and the major type of histology was clear cell RCC ( n = 55; 76.4%). Progressive disease ( n = 25; 34.8%) and irAEs ( n = 22; 30.6%) were the most common causes for discontinuing treatment. Median PFS and OS seemed similar between patients who discontinued treatment because of irAEs and for patients who did not ( p = 0.360 and p = 0.069, respectively). Importantly, for patients with synchronous metastatic disease at diagnosis ( n = 56), nephrectomy before initiating nivolumab plus ipilimumab had a significantly positive impact on better OS when compared to that in patients without nephrectomy ( p = 0.028). Conclusion This study confirms efficacy and safety of nivolumab plus ipilimumab for mRCC patients in real-world settings. Furthermore, nivolumab plus ipilimumab was associated with a better outcome in patients who had undergone nephrectomy at diagnosis for synchronous mRCC.