Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases
Debu Tripathy, Sara M. Tolaney, Andrew D. Seidman, Carey K. Anders, Nuhad K. Ibrahim, Hope S. Rugo, Chris Twelves, Véronique Dièras, Volkmar Müller, Yining Du, Sue Currie, Ute Hoch, Mary Tagliaferri, Alison L. Hannah, Javier Cortés, ATTAIN Investigators, Daphne Tsoi, Susan Chua, Elgene Lim, Craig Underhill, Philip R. Clingan, Arlene Chan, Ines Deleu, Marleen Borms, François P. Duhoux, Ahmad Awada, Marie-Pascale Graas, Jean-Luc Canon, Konstantinos Papadimitriou, Thierry Velu, Maureen Trudeau, Michael P. Thirlwell, Philippe Barthélémy, Miruna Timar David, Delphine Loirat, Mireille Mousseau, Hugues Bourgeois, Jean‐Christophe Théry, Tanja Fehm, Pauline Wimberger, Margarita Tokar, Georgeta Fried, Ido Wolf, Luca Gianni, Marco Colleoni, Michelino De Laurentiis, Francesco Cognetti, Michele Orditura, Carmelo Bengala, Cláudia Vieira, Rita Sousa, Maria de Fatima Cabral da Rocha Cardoso, Josefina Cruz Jurado, José Á. García-Sáenz, Patricia Gomez, Manuel Ruíz‐Borrego, Luis de la Cruz‐Merino, José Manuel Perez Garcia, Pedro Sánchez‐Rovira, Vanesa Ortega, Maria Fernández Abad, Srinivasan Madhusudan, Anne Armstrong, Pavani Chalasani, Lee S. Schwartzberg, Simon Khagi, David A. Potter, Alejandra Perez, Nicole Williams, Michelle Melisko, Eric Harris, Foluso O. Ademuyiwa, Jennifer M. Specht, DiSean Kendall, Robyn L. Young, Petros Nikolinakos, Katherine H. R. Tkaczuk
Abstract
Importance: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM. Objective: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial. Design, Setting, and Participants: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019. Interventions: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). Main Outcomes and Measures: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate. Results: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable. Conclusions and Relevance: The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research. Trial Registration: ClinicalTrials.gov Identifier: NCT02915744.