Characterization of tumor responses in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib in REFLECT.

4078 Background: In REFLECT, lenvatinib was noninferior to sorafenib based on overall survival in pts with uHCC (median 13.6 vs 12.3 mos; hazard ratio [HR] 0.92, 95% CI 0.79–1.06). The objective response rate (ORR) with lenvatinib was 18.8% by blinded independent imaging review (IIR) per RECIST v1.1; ORR was 40.6% by blinded IIR per mRECIST. Here we further characterize the tumor responses in pts with uHCC who were treated with lenvatinib in REFLECT. Methods: Assessments of ORR included all pts randomly assigned to lenvatinib treatment (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight <60 kg). Time to first objective response (TTR) and duration of response (DOR) were calculated among pts who achieved a partial or complete tumor response. Tumors were assessed by IIR per RECIST v1.1 or mRECIST. Median DOR was estimated with the Kaplan-Meier product-limit method; 95% CI was estimated with a generalized Brookmeyer and Crowley method. Results: 478 Pts were randomly assigned to receive lenvatinib. Among the 90 pts (18.8%) who achieved an objective response by IIR per RECIST v1.1, median TTR was 2.8 mos (range 1–29) and median DOR was 7.4 mos (95% CI 5.6–9.2). Of the 194 pts who had an objective response by IIR per mRECIST, median TTR was 1.9 mos (range 1–15) and median DOR was 7.3 mos (95% CI 5.6–7.4). ORRs by selected baseline characteristics are reported in the Table. Notably, among responders by IIR per RECIST v1.1 (n=90), median overall survival (by Simon-Makuch method) was 23.4 mos (95% CI 17.6–26.3), median duration of treatment was 10.3 mos, and 65.6% of pts experienced grade ≥3 treatment-related adverse events. Conclusions: Pts with uHCC treated with lenvatinib achieved objective responses with a similar frequency to those seen with single-agent immune checkpoint inhibitors. These responses occurred irrespective of baseline characteristics. Tumor responses occurred early and were durable. Clinical trial information: NCT01761266. [Table: see text]