Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial

The oncologist

article

Sara A. Hurvitz¹  Larisa Ryvo²  Ming-Shen Dai³  Vladimir Milovanov⁴  Jesús Alarcón⁵  Sujith Kalmadi⁶  Eduardo Cronemberger⁷  Cristiano Souza⁸  Luciana Landeiro⁹  Ron Bose^1,10  Judith Bebchuk^1,11  Cristina Saura^1,12  Fairooz Kabbinavar^1,11  Richard Bryce^1,11  Kiana Keyvanjah^1,11  Adam M. Brufsky^1,13  Mafalda Oliveira^1,12  Maureen E. Trudeau^1,14  Beverly Moy^1,15  Suzette Delaloge^1,16  William Gradishar^1,17  Sung-Bae Kim^1,18  Barbara Haley^1,19 

[1] University of California Los Angeles/Jonsson Comprehensive Cancer Center;Sourasky Medical Center (Ichilov);Tri-Service General Hospital, National Defense Medical Center;Tambov Regional Oncology Center;Hospital Universitario Son Espases;Ironwood Cancer and Research Centers;Centro Regional Integrado de Oncologia;Hospital de Câncer de Barretos;Nucleo de Oncologia Da Bahia;Washington University School of Medicine;Inc.;Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, SOLTI Breast Cancer Cooperative Group;Magee-Womens Hospital of UPMC;Sunnybrook Health Sciences Centre;Massachusetts General Hospital Cancer Center;Gustave Roussy;Robert H. Lurie Comprehensive Cancer Center of Northwestern University;Asan Medical Center, University of Ulsan College of Medicine;University of Texas Southwestern

关键词: Capecitabine;    Central nervous system neoplasms;    Lapatinib;    Neratinib;    Receptor;    ErbB-2;   

DOI  :  10.1002/onco.13830

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m 2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m 2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n  = 51; L + C, n  = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline ( n  = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC. Implications for Practice In a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2-positive brain metastases following antibody-based HER2-directed therapies.

【 授权许可】

CC BY|CC BY-NC