As reported in the Journal of Clinical Oncology by David R. Spigel, MD, and colleagues, the phase III RESILIENT Part 2 trial has shown no overall survival benefit with second-line liposomal irinotecan vs topotecan in patients with small cell lung cancer whose disease progressed on or after first-line platinum-based chemotherapy.

David R. Spigel, MD

Study Details

In the international open-label trial, 461 patients were randomly assigned between August 2019 and February 2021 to receive liposomal irinotecan at 70 mg/m² every 2 weeks in a 6-week cycle (n = 229) or topotecan at 1.5 mg/m² on 5 consecutive days every 3 weeks in a 6-week cycle (n = 232). The primary endpoint of the study was overall survival.

Overall Survival

Median follow-up was 18.4 months. Median overall survival was 7.9 months (95% confidence interval [CI] = 6.9–9.2 months) in the liposomal irinotecan group vs 8.3 months (95% CI = 7.3–9.1 months) in the topotecan group (hazard ratio [HR] = 1.11, 95% CI = 0.90–1.37, P = .31). Rates at 12 and 18 months were 31.1% vs 32.5% and 16.1% vs 20.9%, respectively.

Median progression-free survival on blinded independent central review was 4.0 months (95% CI = 3.0–4.2 months) in the liposomal irinotecan group vs 3.3 months (95% CI = 2.8–4.1 months) in the topotecan group (HR = 0.96, 95% CI = 0.77–1.20, nominal P = .71). A total of 34.9% of patients in the liposomal irinotecan group and 44.0% of those in the topotecan group received subsequent anticancer therapy. Objective response rate on blinded independent central review was 44.1% (95% CI = 37.6%–50.8%) vs 21.6% (95% CI = 16.4%–27.4%), respectively (nominal P < .0001). Median response duration was 4.1 vs 4.2 months.

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 42.0% of the liposomal irinotecan group vs 83.4% of the topotecan group; the most common adverse events were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophils (4.4%) with liposomal irinotecan, and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. Serious adverse events occurred in 46.5% vs 39.5% of patients. Adverse events led to discontinuation of treatment in 10.6% vs 10.3%. Treatment-related death occurred in 1.3% vs 0.9% of patients. 

The investigators concluded: “Liposomal irinotecan and topotecan demonstrated similar median overall survival and progression-free survival in patients with relapsed small cell lung cancer. Although the primary endpoint of overall survival was not met, liposomal irinotecan demonstrated a higher objective response rate than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged.”

Paul A. Bunn, MD, of the University of Colorado School of Medicine, Aurora, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The study was supported by Ipsen. For full disclosures of the study authors, visit ascopubs.org.