FDA Approves Expanded Use of Tykerb

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On January 29, the FDA expanded indications for lapatinib (Tykerb) to include its use in combination with the aromatase inhibitor letrozole (Femara) to treat hormonepositive and HER2-positive advanced breast cancer in postmenopausal women. The new approval was based on data from the phase III EGF30008 clinical trial that showed the addition of lapatinib to letrozole significantly improved progression-free survival (PFS) in this patient population.

The double-blind, multicenter study included 1286 postmenopausal women with estrogen- or progesterone-positive, treatment-naïve, advanced metastatic breast cancer and randomized them to receive letrozole monotherapy or letrozole in combination with lapatinib. Patients in the combination arm received 2.5 mg of letrozole plus 1500 mg of lapatinib daily. The intent-to-treat population in the combination arm saw a nearly 2-month improvement in median PFS compared with those in the placebo group, which was small but significant (hazard ratio [HR], 0.86; P = .026). In the subset of 219 patients with HER2-positive tumors, the addition of lapatinib to letrozole nearly tripled PFS to 35.4 weeks compared with 13.0 weeks for letrozole alone (HR, 0.71; P = .019).

In addition, 48.7% of patients receiving lapatinib experienced stable disease compared with 28.7% receiving placebo (P = .003). Investigators said it is too soon to determine whether the PFS benefit observed with the addition of lapatinib will translate to improved overall survival.

Treatment-related adverse effects observed in the study were similar to those seen in previous studies assessing lapatinib in advanced breast cancer. The most commonly reported adverse effects included diarrhea, rash, nausea, and fatigue. Nine patients discontinued the study after developing grade 3 diarrhea. In earlier studies, lapatinib has been associated with decreased heart function, hepatic damage, and lung tissue inflammation, but no significant cardiac signals were noted in this study.

“This drug combination of Tykerb plus Femara provides women being treated for advanced breast cancer with an important treatment option,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products, FDA’s Center for Drug Evaluation and Research, in a press statement. “This entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells’ ability to grow or spread,” he said. Approximately 60% to 70% of all breast cancers are hormone-receptor positive and between 25% and 30% overexpress HER2.

In 2007, lapatinib was approved in combination with capecitabine (Xeloda) to treat women with HER2-positive advanced breast cancer previously treated with chemotherapy, including an anthracycline and a taxane, and trastuzumab (Herceptin). Tykerb is marketed by GlaxoSmithKline and Femara is marketed by Novartis AG.