Oncology NEWS International. Vol. 15 No. 9

Lapatinib May Up Survival in High-EGFR-Expressing RCC

September 1, 2006

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(Drug information on 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.

Vantage Point

ROBERT A. FIGLIN, MD — In this study, lapatinib monotherapy did not extend time to progression or overall survival, compared with hormonal therapy, in patients with advanced renal cell cancer (RCC). "It is a mistake to pursue EGFR inhibitors as monotherapy in kidney cancer when so many other approaches are more promising," said Dr. Figlin, of UCLA, discussant for the paper. He suggested that EGFR inhibitors might be useful in RCC combined with angiogenesis inhibitors or other agents.

Dr. Figlin noted that lapatinib did improve overall survival in the subgroup of patients whose tumors greatly overexpressed EGFR. He described the subgroup analysis as "hypothesis generating, not hypothesis answering," and said that it needs further examination in randomized clinical trials.

TOPIC INDEX

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Breast Breast (HER2+) Breast (Triple-Negative) CML Colorectal Gastrointestinal GIST Genitourinary Gynecologic Head & Neck	Hematology Kidney (Renal Cell) Leukemia Lung Lymphoma Melanoma Multiple Myeloma Ovarian Prostate Sarcoma
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Bone Metastases End-of-Life Care Palliative Care	Ethics in Oncology Practice Management Practice & Policy

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Lapatinib May Up Survival in High-EGFR-Expressing RCC

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