Liposomal Irinotecan Shows Comparable Efficacy With Topotecan in Relapsed SCLC

Small tumor cancer cells treatment cluster on the health tissue blood vessels side view oncology: © Yuriy - stock.adobe.com

Treatment with liposomal irinotecan injection showed similar data regarding median overall survival (OS) and progression-free survival (PFS) compared with topotecan when used for the treatment of patients with relapsed small cell lung cancer (SCLC), according to findings from the phase 3 RESILIENT trial (NCT03088813).¹

Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. At a median follow-up of 18.4 months, the median OS was 7.9 months in the liposomal irinotecan arm vs 8.3 months in the topotecan arm (HR, 1.11; 95% CI, 0.90-1.37; P =.31), missing the primary end point of the study. Among those given liposomal irinotecan, the median PFS per blinded independent central review (BICR) was 4.0 months compared with 3.3 months for those treated with topotecan (HR, 0.96; 95% CI, 0.77-1.20; nominal P =.71).

While the primary end point of OS was not met, the overall response rate (ORR) per BICR was 44.1% (95% CI, 37.6%-50.8%) and 21.6% (range, 16.4%-27.4%), with liposomal irinotecan vs topotecan, respectively.

“The results of the RESILIENT study underline a persistent need for well-tolerated and efficacious treatment options in the second-line setting. In addition, with increasing uptake of first-line chemoimmunotherapy regimens, there is an emerging requirement to establish the efficacy of second-line therapies in patients who have received these regimens,” wrote study authors in findings published in the Journal of Clinical Oncology.

About the Phase 3 RESILIENT Trial

In the phase 3 RESILIENT trial, investigators sought to compare second-line treatment with liposomal irinotecan to topotecan in patients with SCLC with progression on or after first-line platinum-based chemotherapy. Patients were randomly assigned in a 1:1 fashion and given treatment with intravenous (IV) liposomal irinotecan at a dose of 70 mg/m2 every 2 weeks in a 6-week cycle or IV topotecan given at 1.5 mg/m2 daily for 5 consecutive days, every 3 weeks in a 6-week cycle.

OS was the primary end point of the study, and key secondary end points consisted of ORR and PFS.

A total of 461 patients were enrolled between August 2019 and February 2021, including 229 in the liposomal irinotecan arm and 232 in the topotecan arm. These patients made up the intent-to-treat population. In the safety population, 449 patients were included, with 226 receiving liposomal irinotecan and 223 receiving topotecan.

Between groups, baseline characteristics were generally similar. The median age of patients was 62.0 years (range, 28.0-82.0), 32.1% were women, 79.4% were White, and 74.2% had an ECOG performance status of 1. A total of 57.7% of patients were former smokers, 32.1% were current smokers, and 10.2% had never smoked. The majority of patients (88.7%) had metastatic disease. The proportion of patients with brain and/or central nervous system lesions was 24.5% in the liposomal irinotecan arm vs 32.8% in the topotecan arm

As of data cutoff on February 8, 2022, 7 patients (3.1%) continued to follow the assigned trial regimen in the liposomal irinotecan group vs 3 (1.3%) in the topotecan group. The most common reason for study discontinuation was linked with disease progression, which was seen in 149 patients (65.1%) in the liposomal irinotecan arm and 158 (68.1%) in the topotecan arm.

Safety data from the study showed that 42.0% of patients receiving liposomal irinotecan and 83.4% of patients receiving topotecan had a grade 3 or greater treatment-emergent adverse event (TEAE), with the most commonly observed being 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. Further, liposomal irinotecan had a safety profile consistent with what has previously been reported, and no new safety signals were observed.

A total of 10.6% of patients in the liposomal irinotecan group and 10.3% in the topotecan group had TEAEs which led to treatment discontinuation, and TEAEs leading to dose reduction occurred in 27.9% of patients receiving liposomal irinotecan and 46.6% of those receiving topotecan. Death due to TEAEs occurred in 8.4% of patients given liposomal irinotecan and 4.0% of patients given topotecan, of which 1.3% and 0.9% were deemed to be related to treatment.

“Although the primary end point was not met, liposomal irinotecan demonstrated similar PFS, a doubling of ORR, and reduced incidence of grade ≥3 related TEAEs and TEAE-related discontinuations compared with topotecan. This level of activity together with improved tolerability will support future combinatorial therapy research with liposomal irinotecan,” concluded the study authors.

REFERENCE:

Spigel DR, Dowlati A, Chen Y, et al. 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. Published online April 22, 2024. doi:10.1200/JCO.23.02110