MO01.39 Liposomal Irinotecan in Adults with Small Cell Lung Cancer who Progressed on Platinum-Based Therapy: Subgroup Analyses by Platinum Sensitivity

Most patients with extensive small cell lung cancer (SCLC) develop drug resistance to platinum-based first-line therapy or discontinue for other reasons, and second-line therapies are limited. RESILIENT (ClinicalTrials.gov identifier NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of second-line liposomal irinotecan monotherapy in adults with SCLC who progressed with platinum-based first-line therapy. Preliminary data from RESILIENT part 1 (cut off May 8 2019; ≥ 12 weeks follow-up) showed that liposomal irinotecan 70 mg/m2 free base every 2 weeks was generally well tolerated and had encouraging antitumor activity (Paz-Ares et al. WCLC 2019; OA03.03). Objective response rate (ORR; secondary endpoint) was 44% (11/25 patients). Here we report efficacy analyses in post hoc subgroups by platinum sensitivity. RESILIENT part 1 was an open-label, single-arm study comprising dose-finding and dose-expansion phases. Eligible patients were aged ≥ 18 years, with an Eastern Cooperative Oncology Group performance status score of 0/1 and adequate organ function; a single line of prior immunotherapy was permitted. Participants received liposomal irinotecan 70 mg/m2 or 85 mg/m2 free base every 2 weeks, with disease assessments every 6 weeks (Response Evaluation Criteria in Solid Tumors v1.1). Analyses were undertaken for the dose-finding phase recommended dose in subgroups of platinum-resistant/platinum-sensitive patients (with/without disease progression within 90 days from completion of first-line therapy). During dose finding, 5 patients received liposomal irinotecan 85 mg/m2 (deemed not tolerable owing to dose-limiting toxicity) and 12 received 70 mg/m2 (deemed tolerable; recommended dose for dose-expansion phase in which 13 additional patients were included). Analyses included all 25 patients receiving the recommended dose (mean exposure, 13.95 weeks [median 14.86; standard deviation 7.222]). In the platinum-sensitive subgroup (33.3% men; median age 62.0 years), ORR was 53.3% (8/15 patients) and 12-week disease control rate (DCR12wks) was 60% (9/15 patients); in the platinum-resistant subgroup (50.0% men, median age 58.0 years) both ORR and DCR12wks were 30% (3/10 patients). Overall survival and progression-free survival (secondary endpoints) are not yet mature. ORR and DCR12wks were numerically higher in platinum-sensitive than in platinum-resistant patients with SCLC who had progressed with platinum-based first-line therapy before receiving second-line liposomal irinotecan 70 mg/m2 in this phase 2 study. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial versus topotecan, will provide further data.