RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer
David R. Spigel, Afshin Dowlati, Yuanbin Chen, Alejandro Navarro, James Chih‐Hsin Yang, Goran M. Stojanović, Maria Jové, Patricia Rich, Zoran Andrić, Yi‐Long Wu, Charles M. Rudin, Huanyu Chen, Li Zhang, Stanley M.H. Yeung, Fawzi Benzaghou, Luis Paz‐Ares, Paul A. Bunn, on behalf of the RESILIENT Trial Investigators, Philip Clingan, Theresa Hayes, Craig Underhill, Wim Demey, Frédéric Forget, Marc Lambrechts, Kristiaan Nackaerts, Fabio André Franke, Alan A. Azambuja, Rodrigo Régnier Chemim Guimarães, Josiane Mourão Dias, Víctor Sacristán Santos, Bruno Cezar de Mendonça Uchôa, Gustavo Vasconcelos Alves, Cláudia Vaz de Melo Sette, Minghong Bi, Jiuwei Cui, Jian Fang, Jianhua Shi, Ke Wang, Zhen Wang, Xinmin Yu, C. Dayen, Laurent Greillier, Gilles Quéré, Alexander Baraniskin, Helge Bischoff, Frank Griesinger, Cornelius F. Waller, Tibor Csőszi, Gabriella Gálffy, Ibolya Laczó, György Losonczy, S. Tehenes, Angelo Delmonte, Alessandro Follador, Halina Batura‐Gabryel, Piotr Centkowski, Iwona Danielewicz, Andrzej Każarnowicz, Rodryg Ramlau, Alina Muntean, Cristina Oprean, Michael Schenker, Cristina Tiut, Anghel Adrian Udrea, Andrei Ungureanu, Nina Karaseva, Nikolay Kislov, Elena Poddubskaya, Irina Rozhkova, Ekaterina Solovyeva, Anastasia Zimina, Zoran Andrić, Vladimir Kovčin, Marina Petrović, Zorica Radojević, Goran M. Stojanović, SookHee Hong, Sang‐We Kim, Ki Hyeong Lee, Byoung Yong Shim, M. Alonso Garcìa, Antonio Calles, Vanesa Gutiérrez Calderón, Óscar Juan, B. Massuti Sureda, Alejandro Navarro, Ramon Palmero Sanchez, Luis Paz-Ares Rodríguez, Ching-Liang Ho, Sheng‐Hao Lin, Chien‐Ying Liu, Chih-Hsin Yang, İrfan Çiçin, Mahmut Gümüş, Hakan Harputluoğlu, Mustafa Özgüroğlu, S. Seber, Ahmet Sezer, Hryhoriy Adamchuk, Igor Bondarenko
Abstract
PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m 2 every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m 2 daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade ≥3 related treatment-emergent adverse events (TEAEs). The most common grade ≥3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged.