Background: The L-Expanded Access Program (LEAP) was designed to provide access to L/C for HER2+ patients (pts) who previously received anthracycline, taxane, and trastuzumab. In earlier registration trial, CNS metastases occurred in fewer women receiving L/C therapy compared with C alone. Although L therapy has shown efficacy in brain metastasis (BM), it has not been well elucidated in relationship with the outcomes of systemic disease.

Patients and methods : Enrollment in LEAP lasted between Jan. 2007 and Apr. 2008 at 6 centers in Korea. Exploratory analysis on clinical outcomes of brain metastasis was performed.

Results: Total 187 pts enrolled in LEAP. The median treatment duration of all pts was 19.0 weeks (range, 1.4 — 146.9). The median progression free survival and overall survival (OS) of all pts were 20.0 (95% confidence interval [CI]= 18.6-24.0) and 60.0 (95% CI= 50.3-72.7) weeks, respectively. All patients received prior trastuzumab therapy, and 48.7% received prior capecitabine. Among 58 enrolled pts who had BM diagnosed before start L/C therapy, 55 pts were included for the analysis excluding 3 pts (1-consent withdrawal and 2-<3 weeks trial). Fifteen pts had single BM. Majority were HER2 IHC 3+ or FISH +, and 48% were both ER/PR-. Prior to EAP enrollment, 35 pts underwent whole brain radiation, 10 pts SRS or gamma knife, 3 pts local excision, 1 pt had leptomeningeal disease only receiving intrathecal therapy, and 6 pts did not receive local CNS therapy. Four pts underwent more than one modality of local CNS therapy. Of 50 pts evaluable for response, 9.1%, achieved or remained CR; 45.5% had some degree of shrinkage of BM; 14.5%, no change (SD) ≥6mo; 7.3%, SD <6mo; 14.5% developed PD or recurrence of BM. Median TTP of pts (n=53) with BM on L/C therapy was 30.7 weeks (95% CI=25.0-35.1) and median OS (n=55) was 53.1 weeks (95% CI= 42.3-78.0). From the multivariate analysis, TTP of BM was significantly associated with response of BM (HR, 20.3, 95% CI=7.3-56.0, P<0.001). OS of pts with BM was significantly longer with tumors of ER or PR+ status (HR, 3.10, 95% CI=1.55-6.19, p=0.0014), and who responded in systemic disease and brain (HR, 4.5, 95% CI= 2.2-9.2, P<0.0001). Of remaining 129 pts, 8 pts (6.2%) developed new BM on EAP.

Conclusion: Overall survival of patients with brain metastasis who received lapatinib plus capecitabine was prolonged specifically in responders of both brain and extracranial disease. Patients with hormone receptor positive tumors had longer survival compared with those of hormone receptor negative disease.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-04.