RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer
Authors: Spigel David R. , Dowlati Afshin , Chen Yuanbin , Navarro Alejandro , Yang James Chih-Hsin , Stojanovic Goran , Jove Maria , Rich Patricia , Andric Zoran G. , Wu Yi-Long , Rudin Charles M. , Chen Huanyu , Zhang Li , Yeung Stanley , Benzaghou Fawzi , Paz-Ares Luis , Bunn Paul A. ,   on behalf of the RESILIENT Trial Investigators, Clingan Philip , Hayes Theresa , Underhill Craig , Demey Wim , Forget Frederic , Lambrechts Marc , Nackaerts Kristiaan , André Franke Fabio , Azambuja Alan Arrieira , Guimaraes Rodrigo , Mourao Dias Josiane , Santos Victor , Cezar Uchoa Junior Bruno , Alves Gustavo Vasconcelos , de Melo Sette Claudia Vaz , Bi Minghong , Cui Jiuwei , Fang Jian , Shi Jianhua , Wang Ke , Wang Zhen , Yu Xinmin , Dayen Charles , Greillier Laurent , Quere Gilles , Baraniskin Alexander , Bischoff Helge , Griesinger Frank , Waller Cornelius , Csoszi Tibor , Galffy Gabriella , Laczo Ibolya , Losonczy Gyorgy , Tehenes Sandor , Delmonte Angelo , Follador Alessandro , Batura-Gabryel Halina , Centkowski Piotr , Danielewicz Iwona , Kazarnowicz Andrzej , Ramlau Rodryg , Muntean Alina Simona , Oprean Cristina Marinela , Schenker Michael , Tiut Cristina , Adrian Udrea Anghel , Ungureanu Andrei , Karaseva Nina , Kislov Nikolay , Poddubskaya Elena , Rozhkova Irina , Solovyeva Ekaterina , Zimina Anastasia , Andric Zoran , Kovcin Vladimir , Petrovic Marina , Radojevic Zorica , Stojanovic Goran , Hong SookHee , Kim Sang-We , Lee Ki Hyeong , Shim Byoung Yong , Alonso Garcia Miriam , Calles Blanco Antonio , Calderon Vanesa Gutierrez , Juan Vidal Oscar Jose , Massuti Sureda Bartomeu , Navarro Mendivil Alejandro , Palmero Sanchez Ramon , Paz-Ares Rodriguez Luis , Ho Ching-Liang , Lin Sheng-Hao , Liu Chien-Ying , Yang Chih-Hsin , Cicin Irfan , Gumus Mahmut , Harputluoglu Hakan , Ozguroglu Mustafa , Selcuk Seber Erdogan , Sezer Ahmet , Adamchuk Hryhoriy , Bondarenko Igor , Hotko Yevhen , Kobziev Oleh , Koshelenko Oleksandr , Kurochkin Andriy , Semegen Yuriy , Sinielnikov Ivan , Tarasenko Tetiana , Trukhin Dmytro , Carlisle Jennifer , Carr Laurie , Chaudhry Arvind , Chen Hongbin , Chen Yuanbin , Dowlati Afshin , Duvivier Herbert , Edenfield William , Hussein Maen , Jotte Robert , Jujjavarapu Srinivas , Lingerfelt Brian , McCune Steven , Nagajothi Nagaprasad , Rubin Peter , Scilla Katherine , Spigel David , Srkalovic Gordan , Weise Amy , Zuniga Richard 
Published: April 2024

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/m2 every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m2 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.