Frontline Lenvatinib with Subsequent Therapy Improves Survival in Unresectable HCC

Angel Alsina, MD

Patients with unresectable hepatocellular carcinoma (HCC) who were randomized to first-line lenvatinib (Lenvima), compared with sorafenib (Nexavar), and received subsequent anticancer procedures experienced prolonged overall survival (OS), according to results from the REFLECT trial.

In the post hoc analysis of REFLECT, which was reported on at the 2020 GI Cancers Symposium, held January 23-25, in San Francisco, California, patients treated with lenvatinib demonstrated a median OS of 23.0 months, compared with 9.6 months in those randomized to first-line sorafenib. The hazard ratio (HR) was 0.71, although this difference did not quite achieve statistical significance (95% CI, 0.51-1.01),¹ reported Angel Alsina, MD, surgeon at Tampa General Hospital, and colleagues in a poster presentation.

The 45 responders to first-line lenvatinib who received subsequent nonradiotherapy anticancer procedures had a median OS of 27.2 months. Patients who received subsequent radiotherapy were excluded from the OS analysis due to the focus of radiotherapy on controlling local metastatic tumors, according to the researchers. Because there were only 10 responders to first-line sorafenib, median OS could not be evaluated in this group.

“The evolving HCC treatment landscape now has options beyond a linear progression from locoregional therapy to systemic therapy (as might be suggested by some treatment guidelines) and expands the available scenarios for dynamic treatment sequencing,” the investigators concluded in their poster. “This retrospective analysis of REFLECT demonstrated that improved OS was correlated with subsequent anticancer procedures in patients who received first-line lenvatinib or sorafenib. Among patients who received subsequent anticancer procedures, those randomized to lenvatinib had numerically longer, though not statistically significant, OS compared with patients in the sorafenib arm.”

REFLECT was a phase III study comparing the efficacy and safety of lenvatinib versus sorafenib in the first-line treatment of patients with unresectable HCC. Patients were followed every 12 weeks, starting with the first visit after stopping the study medications until data cutoff (November 13, 2016) or death.²

In the main REFLECT analysis, lenvatinib proved noninferior to sorafenib on the OS endpoint as first-line treatment for unresectable HCC. Median OS was 13.6 and 12.3 months for lenvatinib- and sorafenib-treated patients, respectively.² The post hoc analysis presented at the meeting examined OS between treatment arms during the follow-up period.

Over the follow-up, 252 of the 954 patients in REFLECT (26%) received subsequent anticancer procedures (lenvatinib arm, n = 130; sorafenib arm, n = 122). The most common procedures were transarterial chemoembolization (lenvatinib arm, n = 69; sorafenib arm, n = 81) and hepatic intra-arterial chemotherapy (lenvatinib arm, n = 23; sorafenib arm, n = 25). Procedures used less often were radiofrequency ablation, hepatectomy, percutaneous ethanol injection, cryoablation, and other procedures.

The authors noted a geographic imbalance in the use of subsequent anticancer procedures. Two-thirds of REFLECT patients were from the Asia-Pacific region, but 90% of patients who underwent subsequent anticancer procedures were from this region.

ECOG performance status and laboratory assessments including liver function were comparable between the 2 treatment arms at discontinuation of first-line treatment. Median albumin-bilirubin scores were also similar between the arms at baseline and at the study off-treatment visit.

Patients who received subsequent anticancer procedures and/or medications had longer OS compared with those who did not. In the lenvatinib arm, median OS was 19.5 months in those who received subsequent anticancer procedures and/or medications compared with 17.0 months in the sorafenib-treated patients who received subsequent anticancer therapy (HR, 0.84; 95% CI, 0.67-1.06).

Patients in the lenvatinib arm who did not receive subsequent therapy had a median OS of 10.5 months versus 7.9 months in the sorafenib arm who did not receive such therapy.

References

1. Alsina A, Kudo M, Vogel A, et al. Subsequent anticancer procedures following first-line lenvatinib (LEN): A post hoc analysis from the phase III REFLECT study in unresectable hepatocellular carcinoma (uHCC). Presented at GI Cancers Symposium; January 23-25, 2020; San Francisco, CA. Abstract 520.
2. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

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