Nivolumab+Ipilimumab (PD-1+CTLA-4) Sustains OS Benefit in 1L Unresectable HCC; Deep Responses Track With Long Survival

Nivolumab (PD-1 inhibitor) plus ipilimumab (CTLA-4 inhibitor) was tested vs lenvatinib/sorafenib (TKI SOC options) in the Phase 3 CheckMate-9DW first-line unresectable HCC trial (NCT04039607; n=668), with nivolumab maintenance for ≤2 years. At median follow-up 52.5 months, OS remained improved vs LEN/SOR (HR 0.78, 95% CI 0.65–0.93) with higher BICR ORR (36% vs 13%) and more durable responses; by depth of response, patients achieving tumor shrinkage −60% to ≤−30% had median OS 31.1 months (95% CI 19.9–40.4) on NIVO+IPI vs 20.9 months (15.1–30.9) on LEN/SOR, while those with −100% to ≤−60% had OS not reached in both arms (NR [NE] vs NR [28.3–NE]). Long-term survivors (≥4 years post-randomization) were more frequent with NIVO+IPI (62 vs 33), had higher BICR ORR (76% vs 24%) and CR rate (21% vs 6%), and experienced markedly longer median treatment-free intervals (23.3 vs 0.5 months), with 42% vs 6% remaining off study treatment and free of subsequent therapy; TRAEs in long-term survivors were reported as consistent with the overall population.