Frontline Lenvima Is Noninferior to Standard Therapy in Liver Cancer Trial

Frontline Lenvima (lenvatinib) was not inferior to the current standard therapy, Nexavar (sorafenib), in patients with unresectable hepatocellular carcinoma (HCC), according to Eisai, the developer of the multikinase inhibitor.

In a phase 3 trial, known as Study 304, overall survival (OS) outcomes with Lenvima were noninferior to OS results with Nexavar, meeting the study’s primary endpoint. The findings also demonstrated statistically significant improvements with Lenvima for secondary endpoints, including progression-free survival, time to progression and objective response rate (ORR). Eisai reported that it intends to present the full data at an upcoming scientific meeting and will also discuss the findings with the FDA and global regulatory authorities.

“Although much progress has been made in cancer research, there remains a great need for more options in the treatment of unresectable hepatocellular carcinoma,” Alton Kremer, M.D., Ph.D., chief clinical officer and chief medical officer, Oncology Business Group at Eisai, said in a statement. “The findings from this phase 3 trial represent an important development for previously untreated patients with unresectable hepatocellular carcinoma who unfortunately face a poor prognosis.”

The international, multicenter, open-label, noninferiority Study 304 randomized 954 patients with unresectable HCC to frontline treatment with Lenvima at either 8 mg or 12 mg once per day based on body weight (478 patients) or Nexavar at 400 mg twice daily (476 patients). Patients received treatment until progression or unacceptable toxicity.

The most frequently reported all-grade adverse events in the Lenvima group were hypertension, diarrhea, decreased appetite, weight loss and fatigue. These toxicities are in line with previous side-effect results reported for Lenvima.

Results from a phase 2 study of Lenvima in patients with advanced HCC were published last year in the Journal of Gastroenterology. The study enrolled 46 patients between July 2010 and June 2011 at locations across Japan and Korea. Patients were not eligible for surgery or local therapy.

Lenvima was administered at 12 mg orally once daily in 28-day cycles. The primary endpoint was time to progression (TTP). Secondary endpoints included OS, ORR and disease control rate.

The median TTP was 7.4 months. The ORR was 37 percent, comprising all partial responses (17 patients). Nineteen patients (41 percent) had stable disease and the disease control rate was 78 percent. The median OS was 18.7 months.

The most common all-grade adverse events (AEs) included hypertension (76 percent), palmar-plantar erythrodysesthesia syndrome (65 percent), decreased appetite (61 percent) and proteinuria (61 percent). Seventy-four percent of patients (34 patients) required dose reductions related to AEs and 22 percent of patients (10 patients) discontinued treatment due to AEs. Lower body weight was associated with a higher incidence of early (less than 30 days) dose withdrawal or reduction.

Lenvima is an oral, multitargeted receptor tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFR. It is FDA-approved for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, as well as for use in combination with Afinitor (everolimus) for patients with advanced renal cell carcinoma who were previously treated with an antiangiogenic therapy.