MNGO-17EFFECTS OF LAPATINIB ON MENINGIOMAS IN ADULTS WITH NEUROFIBROMATOSIS TYPE 2 (NF2)

Abstract

BACKGROUND: EGFR and ErbB2 are overexpressed schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ ErbB2 inhibitor, has antitumor activity against schwannomas. METHODS: We conducted a single institution, retrospective review of patients with NF2 and progressive vestibular schwannomas treated on a Phase II clinical trial with lapatinib (NCT00973739). We included patients with at least one volumetrically measurable meningioma (>0.5cm3) who received at least five 28-day courses of therapy. Lapatinib was administered in continuous 4-week courses receiving standard adult doses (1,500mg once daily). Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive meningioma growth and response were defined as +20%/-20%-change from baseline in tumor volume, respectively. Off-treatment defined as any period >5 months without lapatinib. RESULTS: Eight patients (ages: 20-58 years) who met criteria had 17 evaluable meningiomas with a combined volume of 61.35cc baseline, 61.17cc during treatment, and 108.86cc (+77.44%-change) off-treatment. Tumor volume differences were significant (p = 0.0033) using a two-sided Wilcoxon-Signed-Rank test. Median time on-therapy: 15 months and offtherapy: 14 months (both ranged 5-29 months). We calculated a median and mean annual growth rate off-treatment: 10.42% and 20.05%, respectively. The best response to therapy was -26.1% after 23 months on lapatinib. Two of 17 tumors grew >20% on-treatment while 9 of 17 grew >20% off treatment. CONCLUSIONS: These data suggest that lapatinib has modest growth-inhibitory effects on meningiomas in NF2 patients. Prospective studies of lapatinib for NF2 patients with progressive meningiomas may be warranted.