Subsequent anticancer procedures following first-line lenvatinib (LEN): A post hoc analysis from the phase III REFLECT study in unresectable hepatocellular carcinoma (uHCC).

520 Background: The availability of newer therapeutic options has shifted the treatment paradigm for uHCC, evoking questions regarding the sequencing of anticancer therapies. REFLECT was a phase 3 study comparing the efficacy and safety of LEN versus sorafenib (SOR) in first-line treatment of patients (pts) who have uHCC. In this post hoc analysis, we investigated overall survival (OS) during the follow-up survival period between treatment arms for pts who did and did not receive subsequent anticancer procedures and for responders to first-line LEN who received subsequent anticancer procedures. Methods: Pts in REFLECT were randomized 1:1 to LEN or SOR. The follow-up period commenced at the first visit after stopping study medications. Pts were followed-up every 12 weeks until data cutoff (Nov 13, 2016) or death. OS was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). Pts receiving subsequent radiotherapy were excluded from the OS analysis. Results: Of the 954 pts enrolled in REFLECT, 122/478 (26%) LEN- and 130/476 (27%) SOR-treated pts received subsequent anticancer procedures, with the most common being transarterial chemotherapy embolization (LEN n = 69 [14.4%]; SOR n = 81 [17.0%]) and hepatic intra-arterial chemotherapy (LEN n = 23 [4.8%]; SOR n = 25 [5.3%]). Eastern Cooperative Oncology Group performance status scores and laboratory assessments, including liver function, were comparable between arms at first-line treatment discontinuation. Of the pts who received subsequent anticancer procedures, those randomized to first-line LEN (n = 99) had a longer median OS (23.0 vs 19.6 months, respectively; hazard ratio [HR]: 0.71; 95% CI: 0.51–1.01) than those randomized to first-line SOR (n = 112). Responders to first-line LEN who received subsequent anticancer procedures (n = 45) had a median OS of 27.2 months (95% CI: 20.7–29.8). There were too few SOR responders (n = 10) who received subsequent anticancer procedures to evaluate OS. Conclusions: Pts randomized to first-line LEN who received subsequent anticancer procedures had longer OS compared with the similar sequence for pts taking first-line SOR. Clinical trial information: NCT01761266.