RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer

J Clin Oncol. 2024 Jul 1;42(19):2317-2326. doi: 10.1200/JCO.23.02110. Epub 2024 Apr 22.

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/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.

Trial registration: ClinicalTrials.gov NCT03088813.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / adverse effects
  • Irinotecan* / therapeutic use
  • Liposomes*
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Progression-Free Survival
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / mortality
  • Small Cell Lung Carcinoma* / pathology
  • Topoisomerase I Inhibitors / administration & dosage
  • Topoisomerase I Inhibitors / adverse effects
  • Topoisomerase I Inhibitors / therapeutic use
  • Topotecan* / administration & dosage
  • Topotecan* / adverse effects

Substances

  • Topotecan
  • Irinotecan
  • Liposomes
  • Topoisomerase I Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03088813