1. Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial
- Author
-
Sara A. Hurvitz, Maureen E. Trudeau, William J. Gradishar, Larisa Ryvo, Ming-Shen Dai, Sujith Kalmadi, Cristiano Souza, Eduardo Cronemberger, Suzette Delaloge, Adam Brufsky, Mafalda Oliveira, Vladimir Milovanov, Beverly Moy, Sung Bae Kim, Kiana Keyvanjah, J. Alarcón, Fairooz F. Kabbinavar, Ron Bose, Richard A. Bryce, Cristina Saura, Judith Bebchuk, Barbara Haley, Luciana Landeiro, Institut Català de la Salut, [Hurvitz SA] University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, California, USA. [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Cooperative Group, Barcelona, Spain. [Trudeau ME] Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. [Moy B] Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. [Delaloge S] Gustave Roussy, Villejuif, France, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Oncology ,Central Nervous System ,Cancer Research ,Receptor, ErbB-2 ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Neratinib ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,ErbB-2 ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Cumulative incidence ,Other subheadings::/therapeutic use [Other subheadings] ,Receptor, ErbB‐2 ,skin and connective tissue diseases ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Hazard ratio ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Metastatic breast cancer ,Treatment Outcome ,030220 oncology & carcinogenesis ,Quinolines ,Female ,medicine.symptom ,Receptor ,medicine.drug ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Breast Neoplasms ,Lapatinib ,Asymptomatic ,Quimioteràpia combinada ,Capecitabine ,03 medical and health sciences ,Breast cancer ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Internal medicine ,Breast Cancer ,medicine ,Humans ,Oncology & Carcinogenesis ,Otros calificadores::/uso terapéutico [Otros calificadores] ,business.industry ,medicine.disease ,030104 developmental biology ,Central nervous system neoplasms ,Mama - Càncer - Tractament ,Avaluació de resultats (Assistència sanitària) ,business - Abstract
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/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 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., This article reports outcomes among HER2‐positive breast cancer patients with central nervous system metastases at baseline from the phase III NALA trial of neratinib plus capecitabine versus lapatinib plus capecitabine.
- Published
- 2021