WASHINGTON -- The FDA on Thursday for the first-line treatment of hepatocellular carcinoma (HCC) patients with unresectable disease.
Approval was based on the REFLECT study, a multicenter non-inferiority trial, which randomized 954 HCC patients 1:1 to either 8 mg or 12 mg oral lenvatinib (depending on the patient's weight) versus 400 mg sorafenib twice daily until disease progression or unacceptable toxicity. The drug is approved at the 8 mg once-daily dose for patients <60 kg and at the 12 mg once-daily dose for those ≥60 kg.
"Unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade," said Ghassan Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, in a from drugmaker Eisai. "REFLECT is the first-ever positive phase III trial against an active comparator in unresectable HCC."
In terms of median overall survival, the trial showed that lenvatinib was non-inferior to sorafenib (HR 0.92, 95% CI 0.79-1.06). Though not statistically superior, median overall survival was 13.6 months in the lenvatinib-treated group versus 12.3 months in the sorafenib group.
However, progression-free survival based on modified RECIST was significantly improved, at 7.3 months with lenvatinib versus 3.6 months with sorafenib (HR 0.64, 95% CI 0.55-0.75, P<0.001). Overall response, again based on modified RECIST, also favored lenvatinib (41% versus 12%).
"The efficacy and safety data from REFLECT are important findings for oncologists and others in the multidisciplinary teams who treat liver cancer, as well as for our patients who are affected by it," said Abou-Alfa.
The most common adverse events (≥20%) associated with lenvatinib in the trial were abdominal pain, arthralgia/myalgia, diarrhea, decreased appetite, fatigue, hypertension, hand-foot syndrome, hemorrhagic events, hypothyroidism, proteinuria, dysphonia, nausea, and weight loss,
Serious adverse events included hepatic encephalopathy in 5% of lenvatinib-treated patients, hepatic failure and ascites in 3% each, and decreased appetite in 2%.
Lenvatinib was previously approved for advanced thyroid cancer and renal cell carcinoma.