Lapatinib

Key Points

Tykerb Lapatinib GLAXOSMITHKLINE 4-anilinoquinazoline kinase inhibitor approved in combination with capecitabine for the treatment of advanced or metastatic breast cancer

This agent inhibits the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors, thus inhibiting ErbBdriven tumor cell growth. Lapatinib was approved in combination with capecitabine on March 13, 2007, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

Efficacy. The efficacy of lapatinib in combination with capecitabine for the treatment of breast cancer was evaluated in a randomized, phase 3 trial. Eligible patients had HER2 (ErbB2)-overexpressing, locally advanced or metastatic breast cancer that had progressed after prior treatment including anthracyclines, taxanes, and trastuzumab. Patients (N=399) were randomized to receive either lapatinib 1,250 mg once daily (continuously) plus capecitabine 2,000 mg/m²/d on Days 1 to 14 every 21 days (n=198) or capecitabine 2,500 mg/m²/d alone on Days 1 to 14 every 21 days (n=201). The study end point was time to progression (TTP) (time from randomization to tumor progression or death related to breast cancer). The median age of enrolled patients was 53 years; 97% of patients had stage IV breast cancer. An independent assessment demonstrated that the median TTP in patients treated with lapatinib plus capecitabine was 27.1 weeks (95% CI, 17.4–49.4) versus 18.6 weeks (95% CI, 9.1–36.9) in patients treated with capecitabine alone. The investigator assessment of the same end point demonstrated a TTP of 23.9 weeks (95% CI, 12.0–44.0) in patients treated with lapatinib plus capecitabine versus 18.3 weeks (95% CI, 6.9–35.7) in patients treated with capecitabine alone. Independent assessment demonstrated a response rate of 23.7% (95% CI, 18.0%–30.3%) in patients treated with combination therapy versus 13.9% (95% CI, 9.5%–19.5%) in patients treated with capecitabine alone; the investigator assessment demonstrated a response rate of 31.8% (95% CI, 25.4%–38.8%) in patients treated with combination therapy versus 17.4% (95% CI, 12.4%–23.4%) in patients treated with capecitabine alone.

Dosing. The recommended dose of lapatinib is 1,250 mg (5 tablets) taken orally once daily on Days 1 to 21 continuously in combination with capecitabine 2,000 mg/m²/d (taken orally in 2 doses approximately 12 hours apart) on Days 1 to 14 in a repeating 21-day cycle. Lapatinib should be taken ≥1 hour before or after a meal; capecitabine should be taken with food or within 30 minutes after food.

Pricing. Lapatinib is expected to cost approximately $2,900 per month, or approximately $96 per daily dose.