Background: IO agents and TKIs have revolutionized treatment landscape of mRCC pts. Despite robust clinical trials’ data for these agents, real-world (rw) clinical outcomes data, especially from community setting in the US is limited. Methods: This retrospective cohort study included mRCC pts who received 1L treatment with either, pembrolizumab + axitinib (P+A) (IO+TKI), ipilimumab + nivolumab (I+P) (IO+IO) or cabozantinib, sunitinib, pazopanib and axitinib (TKI monotherapy (mono)) between 1/1/2018 and 9/30/2020 from The US Oncology Network of 480 sites. Patients were followed until 12/31/2020 to collect data on rw-time on treatment (rwToT), rw-time to next treatment (rwTTNT) and overall survival (OS). Kaplan-Meier analyses were performed to examine clinical outcomes. Results: We identified 1,538 eligible pts, of which 18% (n = 279) received P+A, 42% (n = 641) I+N and 40% (n = 618) TKI mono. The median follow-up duration for P+A, I+N and TKI mono cohort was 7.2 (range 0.0 - 20.5), 8.5 (range 0.0 - 32.3) and 7.8 (range 0.0 - 35.3) months, respectively. Majority of pts had clear cell histology (P+A - 82%, I+N - 86%, and TKI mono - 72%) and intermediate/poor IMDC risk score (P+A - 87%, I+N - 94%, and TKI mono - 81%). Median OS was not reached for P+A and was similar for I+N and TKI mono cohort (NR, 27.6, and 26.9 months, p=0.237, respectively). The median rwToT (13.6 vs. 5.8 vs. 3.4 months, p<0.0001) and rwTTNT (16.4 vs. 8.3 vs. 8.4 months, p<0.0001) was higher for P+A cohort compared to I+N and TKI mono cohort, respectively. Similar clinical outcomes results were noted for subgroup of pts with intermediate and/or poor IMDC risk score (Table). Conclusions: In this rw US community oncology-based study, longer treatment exposure (rwToT, rwTTNT) was noted in P+A compared to I+N or TKI mono. These rw endpoints may reflect treatment exposure, tolerability and/or compliance.

*NR: Not Reached