First-line immune combination therapies for non-clear cell vs. clear cell metastatic renal cell carcinoma: Real-world multicenter data from Germany

Introduction The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) vs. non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies. Methods Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC vs. ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups, Eastern Cooperative Oncology Group (ECOG) status and sarcomatoid feature. Results Of 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months vs. not reached for ccmRCC vs. nccmRCC patients (p=0.6). Median PFS was 13 vs.15 months (p=0.9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (Hazard Ratio [HR]: 1.23; p=0.6) or a higher progression rate (HR: 1.0; p=1.0). Conclusion In our real-world multi-institutional study, no differences between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed. Micro abstract In our German mutiinstitutional retrospective study of 289 mRCC patients with 39 (13%) patients harbored non-clear cell metastatic renal cell carcinoma, no significant overall or progression-free differences were observed between nccmRCC and clear cell metastatic renal cell carcinoma (ccmRCC) groups undergoing first-line immune combination therapy, indicating similar outcomes regardless of histological type.