Impact of antitumor activity on survival outcomes, and nonconventional benefit, with nivolumab (NIVO) in patients with advanced hepatocellular carcinoma (aHCC): Subanalyses of CheckMate-040.
El-Khoueiry AB., Melero I., Yau TC., Crocenzi TS., Kudo M., Hsu C., Choo S., Trojan J., Welling T., Meyer T., Kang Y-K., Yeo W., Chopra A., Zhao H., Baakili A., Dela Cruz CM., Sangro B.
475 Background: NIVO (anti–PD-1 mAb) has demonstrated durable responses, long-term OS, and manageable safety in pts with aHCC in CheckMate-040 (El-Khoueiry, Sangro et al. 2017). With anti–PD-1 therapies, meaningful OS benefit may be seen even in pts who do not achieve a conventional response by RECIST v1.1. Here we report nonconventional benefit with NIVO and effect of antitumor activity on OS in sorafenib-experienced (sor-exp) pts with aHCC, including pts with a best overall response (BOR) of progressive disease (PD). Methods: Sor-exp pts received NIVO (3 mg/kg Q2W) in a phase 1/2 dose-expansion cohort regardless of PD-L1 status. Impact of antitumor activity on median OS (mOS) was determined by calculating change in target lesion size from baseline using quartile analyses (25% cutoff). Nonconventional benefit was analyzed by reductions or stabilizations in target lesion size after progression in pts with a BOR of PD. Results: Sor-exp pts (N=145) had a median follow-up of 14.9 mo. The ORR (RECIST v1.1) was 14% and the DCR was 56%. Median duration of stable disease (SD) was 4.3 mo and the DCR with SD ≥6 mo was 27%. Overall, mOS was 15.6 mo. Degree of OS benefit corresponded with antitumor activity in pts with decreases (≥25%, mOS not reached; 0–25%, mOS 17.7 mo) or increases (0–25%, mOS 11.7 mo; ≥25%, mOS 8.9 mo) in target lesion size (Table). In non-responders (n=124; including pts with BOR of SD or PD), mOS was 13.4 mo. Nonconventional benefit was observed in 11 of 56 pts (20%) with a BOR of PD. Updated clinical data with additional follow-up will be presented. Conclusions: In sor-exp pts, mOS with NIVO corresponded to degree of antitumor activity, with OS benefit not limited to RECIST v1.1 responders. Improved OS in non-responders is likely due to nonconventional benefit, supported by disease reduction or stabilization even in pts with a BOR of PD. Clinical trial information: NCT01658878. [Table: see text]