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from ASCO--the latest on lapatinib for IBC
Lapatinib Shows Promise in Inflammatory Breast Cancer: Presented at ASCO
CHICAGO — June 5, 2008 — Lapatinib monotherapy shows therapeutic promise in relapsed/refractory human epidermal growth factor receptor 2 (HER2)-positive inflammatory breast cancer (IBC) for this difficult to treat disease, researchers reported on June 2 at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.
The study is the first prospective clinical trial conducted in HER2-positive IBC.
"Since inflammatory breast cancer is an aggressive cancer, and often so far advanced at diagnosis that we have few treatments to offer, we are pleased at the results of this study," said investigator and presenter Bella Kaufman, MD, Chaim Sheba Medical Center, Tel Hashomer, Israel.
According to the researchers, IBC is an uncommon (2% to 6%) form of breast cancer with a significantly worse prognosis than other breast cancers.
Lapatinib is a reversible, oral small-molecule inhibitor of epidermal growth factor receptor (EGFR) and receptors HER-2/neu tyrosine kinases.
ASCO 2008: ABSTRACT #636: Clinical activity of lapatinib monotherapy in patients with HER2+ relapsed/refractory inflammatory breast cancer (IBC): Final results of the expanded HER2+ cohort in EGF103009
American Society of Clinical Oncology
Background: IBC is an uncommon (~2-6%) form of breast cancer with a significantly worse prognosis than non-IBC. Lapatinib is a reversible, oral small molecule inhibitor of EGFR and HER-2/neu tyrosine kinases (also known as ERBB1 and ERBB2, respectively). EGF103009 was initially designed as a two stage, Green-Dahlberg study of lapatinib monotherapy in 30 subjects in each of two cohorts, HER2+ and EGFR+/HER2-. Following a 50% response rate in the first 30 HER2+ patients, this cohort was expanded to 120 patients in order to improve the precision of estimated ORR; this represents the only prospective clinical study ever conducted in HER2+ IBC.
Methods: Patients with HER2+ (IHC 3+ / FISH Ampified) IBC that was refractory to anthracyclines, taxanes, and trastuzumab (where available) were enrolled. Pretreatment and day 28 fresh biopsies were collected for each subject to assay for relevant biomarkers. Patients received lapatinib daily (1,500 mg/d). Skin lesions were assessed at 4 week intervals and RECIST-measurable disease if present was assessed at 8 week intervals.
Results: One hundred twenty-six HER2+ patients were treated continuously with once-daily lapatinib (1,500 mg). Final analysis is currently underway and preliminary data suggest a response rate of approximately 40%; responses were also seen in the ~50% of patients who were trastuzumab-refractory. Most frequent toxicity was Grade I/II diarrhea and skin rash. Biomarker analyses of pretreatment tumor biopsies confirmed a molecular phenotype consistent with IBC (i.e., RhoC- and E-cadherin-overexpression); co-expression of pHER2 and pHER3 were predictive of lapatinib response.
Conclusions: Lapatinib monotherapy is active in the treatment of relapsed / refractory HER2+ IBC where few effective therapies are available, and is well tolerated. Within this group, tumors that have an activated HER2/HER3 pathway appear to be more likely to respond. Final analysis of responses and their durability as well as of biomarkers predictive of responses will be presented.
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