Pooled analysis of diarrhea events in patients with cancer treated with lapatinib.

PURPOSE: To characterize diarrhea events in patients with cancer treated with lapatinib as monotherapy or in combination with capecitabine or taxanes. PATIENTS AND METHODS: Eleven clinical trials (phase I, II, or III) in patients with metastatic cancer were analyzed. Lapatinib was administered at doses ranging from 1,000 to 1,500 mg/day as monotherapy (n = 926) or in combination with capecitabine (n = 198) or taxanes (n = 687). Diarrhea events were characterized based on severity, time to onset, duration, required interventions, and clinical outcomes. RESULTS: In the pooled analysis of nine studies, diarrhea occurred in 55% of lapatinib-treated patients and 24% of patients not receiving lapatinib. All grade diarrhea occurred in 51% of patients treated with lapatinib monotherapy and 65% treated with lapatinib plus capecitabine. In a separate analysis, 48% of patients treated with lapatinib plus a taxane experienced diarrhea. Overall, most diarrhea events were grade 1/2. Grade 3 events occurred in <10% of patients and grade 4 events were rare (

Lapatinib in combination with capecitabine in the management of ErbB2-positive (HER2-positive) advanced breast cancer.

Lapatinib is an oral, reversible, dual inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and human epidermal growth factor receptor type 2 ErbB2 (HER2). Results of a phase III study comparing lapatinib plus capecitabine with capecitabine alone in women with ErbB2-overexpressing advanced breast cancer previously treated with an anthracycline, a taxane, and trastuzumab were reported early based on superiority of the combination in prolonging time to tumor progression (TTP). An updated analysis in 399 women supports the earlier findings. In this updated analysis, TTP (hazard ratio [HR] 0.57) favored lapatinib plus capecitabine. Survival trended in favor of the combination. The incidence of cardiac events was numerically higher in the combination arm (5 cases in the combination arm, 2 cases in the monotherapy arm).