Clinical

Lapatinib shows little activity against advanced hepatocellular carcinoma

Last Updated: 2009-09-15 13:40:23 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Lapatinib, an inhibitor of epidermal growth factor receptor (EGFR) and HER2/NEU, has only minimal activity against advanced hepatocellular carcinoma (HCC) and benefits only a subset of patients.

In the September 15th Clinical Cancer Research, Dr. Tanios Bekaii-Saab from The Ohio State University, Columbus, and colleagues report on a multicenter phase II efficacy and tolerability trial of lapatinib, 1500 mg/day in 28-day cycles, in 26 patients with advanced HCC.

The primary end point was the proportion of patients with an objective response as defined by the Response Evaluation Criteria in Solid Tumors.

No patient had an objective response, the authors report.

Median progression-free survival was 1.9 months, and median overall survival was 12.6 months. Patients who developed a rash in response to treatment had a median progression-free survival of 2.4 months and a median overall survival of 16.2 months. For overall survival, the difference between the groups with and without a rash reached "borderline" significance.

The most common toxicities included diarrhea, nausea, and rash. Only 3 patients developed grade 3 toxicities, all of which were reversible.

In contrast to previous findings, this study showed no somatic mutations in HER2/NEU in tissue or blood specimens, and no somatic mutations in EGFR.

"Dual EGFR inhibition with lapatinib has minimal activity in hepatocellular carcinoma," the investigators conclude, "although certain subgroups of patients (such as those who developed a rash, an effect attributable to EGFR/HER1 inhibition) had a more favorable outcome."

In a prepared statement, Dr. Bekaii-Saab said, "Our findings suggest a potential benefit from EGFR inhibition. Overall, though, we were certainly hopeful that lapatinib would be more active and were somewhat disappointed by the results."

Clin Cancer Res 2009;15:5895-5901.