Is liposomal irinotecan superior to topotecan in relapsed small cell lung cancer?
Treatment with liposomal irinotecan in adults with relapsed small cell lung cancer (SCLC) achieves similar overall survival (OS) when compared with topotecan, but the former is associated with a higher overall response rate (ORR), according to the results of RESILIENT, randomized, open-label phase III trial.
“The safety profile of liposomal irinotecan was consistent with its known safety profile, and no new safety concerns emerged,” said the researchers, led by Charles M Rudin from the Memorial Sloan Kettering Cancer Center in New York, US, who presented these findings at ELCC 2023 held at Copenhagen, Denmark.
Rudin and his team assessed eligible patients with histologically or cytologically confirmed SCLC and radiologically confirmed disease progression despite first-line platinum-based chemotherapy. They randomized participants to receive intravenous liposomal irinotecan (70 mg/m2, every 2 weeks in a 6-week cycle) or topotecan (1.5 mg/m2/day for 5 days, every 3 weeks in a 6-week cycle).
Log-rank test stratified by region and platinum sensitivity, with 1-sided significance of 0.023, was performed to assess OS, the primary endpoint. Secondary endpoints were progression-free survival (PFS) and ORR per blinded independent central reviewer.
Of the 461 patients (median age 62.0 years, 67.9 percent men, 74.2 percent ECOG performance status 1) who met the inclusion criteria, 229 received liposomal irinotecan and 232 topotecan. The median follow-up was 18.4 months. [ELCC 2023, abstract 161O]
Majority (88.7 percent) of the patients had metastatic disease. Sites of metastases were as follows: brain or central nervous system (28.6 percent), hepatic (6.9 percent), and bone and locomotor (23.6 percent). Patients also received prior treatment with radiotherapy (51.0 percent), immunotherapy (18.4 percent), and targeted therapy (0.4 percent). [https://www.cancernetwork.com/view/liposomal-irinotecan-yields-high-responses-similar-os-vs-topotecan-in-sclc]
Treatment with liposomal irinotecan resulted in a median OS of 7.9 months and PFS of 4.0 months compared with 8.3 months and 3.3 months with topotecan, respectively. The hazard ratio (HR) for death was 1.11 (95 percent confidence interval [CI], 0.90‒1.37; p=0.3094) with irinotecan, while the HR for disease progression or death was 0.96 (95 percent CI, 0.77‒1.20; p=0.7053).
Notably, patients on liposomal irinotecan achieved higher ORR relative to that with topotecan (44.1 percent vs 21.6 percent).
Additionally, grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 62.4 percent of patients on irinotecan and 87.9 percent of those who received topotecan. TEAEs in the former cohort included neutropenia (8.0 percent), leukopenia (4.0 percent), diarrhoea (13.7 percent), anaemia (2.7 percent), and thrombocytopenia (0.4 percent), among others.
“The phase III RESILIENT study showed similar median OS and PFS for liposomal irinotecan compared with topotecan in patients with SCLC that had progressed on or after first-line platinum-based chemotherapy,” said Rudin. “Although the primary endpoint of OS was not met, liposomal irinotecan was associated with higher ORR compared with topotecan.”
A rapidly progressive lung cancer, SCLC accounts for 15 percent of all lung cancers, according to the researchers. [Cancer 2015;121:664-672; Front Oncol 2019;9:404]