Primary resistance to nivolumab plus ipilimumab therapy affects second-line treatment outcomes in patients with metastatic renal cell carcinoma.

Nivolumab plus ipilimumab (NIVO+IPI) has a long-term response rate of 30% for patients with metastatic renal cell carcinoma (mRCC). However, 20% of patients develop primary resistant disease (PRD) to NIVO+IPI and show poor survival outcomes. In this study, we aimed to evaluate the effect of PRD as a second-line treatment in patients with mRCC. The data used in this multi-institutional, retrospective cohort were collected between August 2015 and January 2023. In total, 189 patients with mRCC were treated with NIVO+IPI and then with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Associations between PRD and progression-free survival of second-line treatment (PFS), progression-free survival 2 (PFS2), and overall survival (OS) were analyzed. The median age at NIVO+IPI initiation was 67 years in the male-dominant population (n = 140, 74.1%), and most patients had clear cell histology (n = 140, 74.1%). PRD was recorded in 42 (22.2%) of 189 patients during NIVO+IPI therapy. Patients who experienced PRD showed poor PFS (hazard ratio [HR], 1.788; 95% confidence interval [CI], 1.176-2.718; p = 0.007), PFS2 (HR, 4.127; 95% CI, 2.649-6.431; p < 0.001), and OS (HR, 3.330; 95% CI, 2.040-5.437; p < 0.001). Before starting second-line therapy, patients with PRD tended to have a poor performance status compared with non-PRD patients and a higher IMDC risk. Second-line drug therapy was not associated with treatment outcomes in patients with PRD. PRD in patients with mRCC receiving NIVO+IPI as first-line treatment was associated with poor clinical course, even with second-line therapy.

Cancer science. 2024 Nov 17 [Epub ahead of print]

Kanami Mori, Kazuyuki Numakura, Yuto Matsushita, Takahiro Kojima, Takahiro Osawa, Tomokazu Sazuka, Shingo Hatakeyama, Keisuke Goto, Kazutoshi Yamana, Shuya Kandori, Takahiro Kimura, Naotaka Nishiyama, Yukari Bando, Kazutoshi Fujita, Kosuke Ueda, Hajime Tanaka, Ryotaro Tomida, Toshifumi Kurahashi, Hiroshi Kitamura, Hideaki Miyake, Tomonori Habuchi

Department of Urology, Akita University Graduate School of Medicine, Akita, Japan., Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan., Department of Urology, Aichi Cancer Center, Nagoya, Japan., Department of Renal and Genitourinary Surgery, Hokkaido University, Sapporo, Japan., Department of Urology, Graduate School of Medicine and School of Medicine, Chiba University, Chiba, Japan., Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan., Department of Urology, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan., Department of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan., Department of Urology, Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan., Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan., Department of Urology, Kindai University Faculty of Medicine, Osaka-sayama, Japan., Department of Urology, Kurume University School of Medicine, Kurume, Japan., Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan., Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan., Department of Urology, Hyogo Prefectural Cancer Center, Akashi, Japan.