LBA11 - Cerebel (EGF111438): An Open Label Randomized Phase III Study Comparing the Incidence of CNS Metastases in Patients (PTS) with HER2+ Metastatic Breast Cancer (MBC), Treated with Lapatinib Plus Capecitabine (LC) Versus Trastuzumab Plus Capecitabine (TC)

Abstract

ABSTRACT Background In HER2+ MBC, central nervous system (CNS) metastases (mets) occur in 28 - 43% of cases. Systemic therapies with potential to prevent or reduce CNS mets are of current interest. Based on lapatinib promising activity in CNS mets, CEREBEL evaluated the prophylactic impact on CNS mets incidence in HER2+ MBC pts treated with Lapatinib plus capecitabine (LC) in comparison to Trastuzumab plus capecitabine (TC). Methods CEREBEL was a multicenter study in HER2+ MBC pts without CNS mets at baseline, confirmed centrally by MRI. Prior treatment must include anthracyclines or taxanes in (neo)adjuvant or metastatic setting. Pts were randomized to LC (L-1250 mg daily + C-2000 mg/m2/day for 14 days [21-day cycle]) or TC (T loading dose 8 mg/kg followed by 6 mg/kg q3weekly + C-2500 mg/m2/day for 14 days [21-day cycle]). Primary endpoint was incidence of CNS as first site of relapse. Secondary endpoints were progression free survival (PFS), overall survival (OS), CNS progression at any time, overall response rate (ORR), clinical benefit response rate, duration of response and safety. Results A pre-specified interim analysis (IA) including 475 pts was performed by an IDMC convened on June 2012. A total of 43% and 46% of pts had not received prior treatment for MBC, 38% and 40% of pts had not received prior T, in LC and TC arms, respectively. Adverse events were similar in both arms with the exception of diarrhoea, nausea and rash (higher with LC). The incidence of CNS metastasis as site of first relapse was 3% for LC versus 4% for TC (OR 95% CI = 0.75 (0.25, 2.20) in modified ITT population (N = 218 pts per arm). The median PFS was 6.6 and 8.0 months in LC and TC arms (HR: 1.3; 95% CI: 1.0, 1.7; ) and median OS was 22.4 and 27.3 months (HR:1.58; 95% CI:1.07,2.32)(ITT) Conclusions Based on these results, the IDMC recommended study termination. Final results and updated survival data will be presented at ESMO with the 535 patients included in CEREBEL. EudraCT number 2008-000673-38 Disclosure X. Pivot: I am consultant and I have received honorariums for the sponsor GSK. R. Allerton: Roche advisory boad for use of Pertuzumab in breast cancer. R. Parikh: Employee of GSK M. DeSilvio: Employee of GSK S. Santillana: Employees of GSK, Director Clinical Development R. Swaby: Employee of GSK. All other authors have declared no conflicts of interest.