Treatment beyond progression after early radiographic changes on first-line ipilimumab/nivolumab in metastatic clear cell renal cell carcinoma.

e16506 Background: Ipilimumab/nivolumab (I/N) is a standard first-line (1L) regimen for metastatic clear cell renal cell carcinoma (mccRCC) with durable benefit in patients achieving deep responses. However, management of patients with mixed responses or early radiographic progression remains undefined, with limited data supporting the common practice of treatment beyond progression (TBP). We evaluated treatment patterns and clinical outcomes associated with TBP following early radiographic changes in I/N-treated patients with mccRCC. Methods: We retrospectively analyzed patients with mccRCC who completed four doses of 1L I/N at Memorial Sloan Kettering Cancer Center. Patients with clinician-assessed mixed response (concurrent regression of some lesions with progression or new lesions) or radiographic progression (overall increase in tumor burden and/or new lesions) on 1st post-induction scan were classified as TBP or not, while those without progression were categorized as early disease control (DC). Kaplan–Meier methods estimated time from 1st post-induction scan to start of next therapy (TTNT) or death (OS), with prespecified landmark estimates at 24 months (TTNT) and 5 years (OS) used for between-group comparisons by log-rank tests. Time on treatment beyond progression (TTBP) was calculated for TBP patients. Results: Among 137 patients completing I/N induction, 54 achieved DC and 83 had mixed response (n=43) or progression (n=40) at 1st post-induction imaging; 47/83 (57%) continued TBP. Among TBP patients, 18 (38%) achieved DC on 2nd scan, (median interscan interval 10.1 weeks), 13 (28%) had further growth, and 6 lacked evaluable 2nd scans. Median TTBP was 12.3 months (CI, 3.8–18.0), and 16 TBP patients (34%) had not received subsequent therapy at last follow-up. At 24 months, TTNT was 12% for no-TBP, 38% for TBP, and 74% for DC (p<0.001). At 5 years, OS was 23% (95% CI, 12–37) for no-TBP, 50% (95% CI, 32–66) for TBP, and 65% (95% CI, 42–80) for DC (p<0.001). Conclusions: In this real-world cohort, TBP after I/N induction was common, with 38% of patients achieving DC and over half remaining on therapy for ≥1 year. However, outcomes with TBP were inferior to those with clear radiographic DC, and long-term benefits for this regimen were rarely observed in TBP patients, including those achieving DC. These findings highlight heterogeneity of early imaging outcomes and support prospective refinement of patient selection for TBP. Second-scan outcomes by first-scan response after I/N induction (n=137; 131 with evaluable second scan). 1st scan category Response on 2nd scan Stable disease on 2nd scan Mixed response on 2nd scan Progression on 2nd scan Total Response 17 (14%) 16 (39%) 4 (10%) 4 (10%) 41 Stable disease 2 (15%) 6 (46%) 3 (23%) 2 (15%) 13 Mixed response 16 (37%) 4 (9%) 16 (37%) 7 (16%) 43 Progression 12 (30%) 5 (12%) 5 (12%) 12 (30%) 34 Total 47 31 28 25 131