LANDSCAPE: An FNCLCC phase II study with lapatinib (L) and capecitabine (C) in patients with brain metastases (BM) from HER2-positive (+) metastatic breast cancer (MBC) before whole-brain radiotherapy (WBR).

Abstract

509 Background: With an incidence of 30%-40%, BM are common complications of HER2+ MBC. Their therapeutic management remains a challenge. As responses on central nervous system (CNS) localization have been reported with L+C combination after WBR, we sought to evaluate the clinical interest of this combination as 1st line treatment for BM in HER2+ MBC patients (pts) with the aim to avoid or to delay WBR. Methods: Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1-14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms, or progressive extra-CNS disease. Using a Simon’s optimal two-stage design with a minimum interesting CNS-OR rate of 20%, 41 evaluable patients were needed. Secondary endpoints included: time to progression (TTP) for both CNS and extra CNS disease; time to WBR; prognostic and predictive value of circulating tumor cells (CTC) and toxicity. Results: From 04 /2009 to 08/2010, 45 pts were enrolled. Median age was 56 (range 35 to 79), 37 pts had multiple metastatic sites, PS was 0 (17 pts), 1 (25 pts) or 2 (2 pts); 36 pts had two or more BM and 42 had previously received trastuzumab. 41 pts received at least 2 cycles of study treatment. 43 pts were evaluable for efficacy endpoints, with a median follow-up of 10 months (range 2.9-16.5). The CNS-OR rate was 67% (95%CI 51-81), with a median time from inclusion to response of 1.8 month. Median TTP was 5.5 months (95% CI 3.9-5.9) and median time to WBR was 8.3 months (95% CI 5.1-11.7). At baseline, 21/42 pts had ≥ 1CTC, vs 7/39 at day 21, p<0.01 (correlation study ongoing). 20 patients (44%) experienced grade 3 or 4 treatment related toxicity, treatment was discontinued due to toxicity in 3 pts. At the time of analysis, 21 pts had received WBR and 10 pts had died. Conclusions: With a high response rate, L + C is an active treatment option and a viable alternative to immediate WBR for HER2+ MBC pts with newly diagnosed BM.