ATLANTA—The investigational agent lapatinib (Tykerb, GlaxoSmithKline) extended survival in the 61% of renal cell carcinoma (RCC) patients whose tumors overexpressed EGFR at the 3+ level, Alain Ravaud, MD, PhD, said at the American Society of Clinical Oncology 42nd Annual Meeting (abstract 4502). Lapatinib is an inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 (also known as HER2) tyrosine kinases. [See ONI June 2006, pg 1 for a report of lapatinib in metastatic HER2-positive breast cancer.] Dr. Ravaud, of University Hospital of Bordeaux, France, reported results of a randomized, open-label phase III trial comparing lapatinib with hormonal therapy in RCC patients for whom first-line cytokine treatment had failed.

"Although additional clinical trials are necessary, our findings suggest that lapatinib could be a new treatment option, along with immunological therapies and antiangiogenesis agents, for patients with advanced renal cell carcinoma that produces high levels of EGFR," Dr. Ravaud said. However, this conclusion was based on a subgroup analysis, and the trial failed to meet its primary endpoint of improved time to progression (TTP).

Patients with advanced renal cell cancer of any histology were randomized to receive oral lapatinib 1,250 mg/d or hormonal therapy (megestrol acetate or tamoxifen, which were standard treatment in 2002 when the trial was designed). Dr. Ravaud said that at the time of the TTP analysis, 417 patients had been randomized, and 298 TTP events had been reported. At that point, neither median TTP nor median overall survival (OS) differed significantly between the lapatinib and hormone therapy groups.

Subgroup Analysis

In subgroup analysis, there was no significant effect of lapatinib in patients who overexpressed EGFR at the 2+ level (by IHC), but those who overexpressed EGFR at the 3+ level (n = 241) had significantly longer median OS (46 weeks vs 37.9 weeks, HR 0.69, P = .019) and showed a trend toward longer TTP (15.1 weeks vs 10.9 weeks, HR 0.76, P = .063). Dr. Ravaud said that additional biomarker evaluation, including FISH, is underway.

No unexpected toxicities were observed, he said. The drug-related adverse effects for lapatinib included rash (44% vs 3% with hormonal therapy) and diarrhea (40% vs 3%). Dr. Ravaud added that 10 patients receiving lapatinib had grade 3-4 diarrhea.

"The EGFR/ErbB2 dual targeted inhibitor, lapatinib, appears to prolong overall survival, compared to hormone therapy, in advanced RCC patients with overexpressed EGFR who failed prior therapy," Dr. Ravaud concluded.