FDA Drug Approval Summary: Lapatinib in Combination with Capecitabine for Previously Treated Metastatic Breast Cancer That Overexpresses HER-2

Abstract

After completing this course, the reader should be able to:1. Describe the clinical trial that led to the approval of lapatinib in combination with capecitabine for the treatment of previously treated patients with HER-2-overexpressing metastatic breast cancer.2. Determine appropriate patients to receive lapatinib plus capecitabine treatment.3. Assess and manage the toxicities of lapatinib plus capecitabine treatment.This article is available for continuing medical education credit at CME.TheOncologist.com. ter TTP results of a prespecified interim analysis were made available, study enrollment was discontinued (399 patients enrolled). CME CME ABSTRACTThe median TTP was 27.1 versus 18.6 weeks (hazard ratio, 0.57; p ‫؍‬ .00013) favoring the lapatinib plus capecitabine arm. Response rates were 23.7% (lapatinib plus capecitabine) versus 13.9% (capecitabine alone). Survival data were not mature.Although the toxicities observed in the lapatinib and capecitabine combination arm were generally similar to those in the capecitabine alone arm, a higher incidence of diarrhea and rash was noted with the combination. Grade 3 or 4 adverse reactions that occurred with a frequency of >5% in patients on the combination arm were diarrhea (13%) and palmar-plantar erythrodysesthesia (12%). There was a 2% incidence of reversible decreased left ventricular function in the combination arm.

Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I–Induced Breast Cancer Cell Functions

“…Current strategies targeting the IGF system in disease states such as cancer include monoclonal antibodies directed against the receptor, tyrosine kinase inhibitors or anti-ligand (anti-IGF-I) antibodies (6). These, however, have proven to be unsuccessful in large-scale clinical trials (7).…”

Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism

“…Treatment-associated elevations in transaminases and bilirubin have been reported with other tyrosine kinase inhibitors including sunitinib, lapatinib, and erlotinib (Motzer et al, 2007;Loriot et al, 2008;Ryan et al, 2008), and the incidence varies with agent. It is possible that these treatment-associated elevations in liver enzymes observed with tyrosine kinase inhibitors reflect overlapping on-target and off-target class effects; however, specific mechanisms remain to be elucidated.…”

Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases – the UK experience

“…The global lapatinib expanded access programme (LEAP) study was a single-arm open-label clinical trial that allowed access to lapatinib in combination with capecitabine for patients with HER2 overexpressing breast cancers, who had previously received anthracycline, taxane and trastuzumab, with the aim of providing clinical benefit while awaiting regulatory approval in individual countries, and further validating safety data observed in EGF100151 in a larger population (Ryan et al, 2008). Entry criteria were similar to those in the pivotal trial; in contrast, however, earlier capectabine use was permitted and patients with cerebral metastatic disease could participate, provided they were on a steroid dose of p2 mg per day of dexamethasone (or equivalent) and had a performance status (PS) of 0 to 2.…”