Similar overall survival with liposomal irinotecan vs. topotecan in patients with SCLC who previously received platinum-based chemotherapy
The phase III RESILIENT trial did not meet its primary endpoint of improved overall survival (OS) with liposomal irinotecan compared to topotecan in patients with small cell lung cancer (SCLC) who have progressed on or after platinum-based first-line therapy. However, a doubling of the secondary endpoint of objective response rate (ORR) in favour of liposomal irinotecan was observed.
Small-cell lung cancer (SCLC) is a rapidly progressive lung cancer that accounts for 15% of all lung cancers. Liposomal irinotecan encapsulates irinotecan in a lipid-bilayer vesicle, leading to prolonged circulation, protection from hydrolysis and rapid metabolic conversion. RESILIENT is a two-part phase II/III study to assess the safety, tolerability and efficacy of second-line liposomal irinotecan monotherapy versus topotecan in patients with SCLC. In part 1, liposomal irinotecan (70 mg/m2) demonstrated promising antitumour activity, with no new safety signals. At ELCC 2023, results from part 2 were presented.
Eligible patients with histologically or cytologically confirmed SCLC and radiologically confirmed disease progression despite first-line platinum-based chemotherapy were randomised (1:1) 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). The primary endpoint of overall survival (OS) was evaluated by log-rank test (stratified by region and platinum sensitivity) with 1-sided significance of 0.023. Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) per blinded independent central review (BICR).
In total, 229 patients were randomised to liposomal irinotecan and 232 to topotecan. Median age was 62.3 years, 32.1% were female, 74.2% had an ECOG performance status of 1 and 88.7% had metastatic disease. After a median follow-up of 18.4 months, median OS was 7.9 months for patients in the liposomal irinotecan arm and 8.3 months for patients receiving topotecan (HR[95%CI]: 1.11[0.90-1.37], p= 0.3094). Furthermore, also PFS was comparable in the liposomal irinotecan and topotecan arms (median PFS of respectively 4.0 vs. 3.3 months, HR[95%CI]: 0.96[0.77-1.20], p= 0.7053). In contrast, the ORR doubled for patients receiving liposomal irinotecan as compared to patients receiving topotecan (44.1% vs. 21.6%, p< 0.0001). Complete response rates in the liposomal irinotecan and topotecan arms were respectively 5.2% and 3.0%. Median duration of response was highly comparable at 4.1 and 4.2 months. In total, 62.4% of patients in the liposomal irinotecan arm experienced treatment-emergent adverse events (TEAEs) of grade ≥3, as compared to 87.9% of patients treated with topotecan. TEAEs led to treatment discontinuation in respectively 10.6% and 10.3% of patients. The most common grade ≥3 TEAEs in the liposomal irinotecan arm were diarrhoea (13.7%), neutropenia (8.0%), decreased neutrophil count (4.4%), leukopenia (4.0%) and decreased white blood cell count (4.0%).
The phase III RESILIENT study demonstrated similar median OS and PFS for liposomal irinotecan and topotecan in patients with SCLC that had progressed on or after first-line platinum-based chemotherapy. Although the primary endpoint of OS was not met, liposomal irinotecan was associated with higher ORR compared with topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile and no new safety concerns were identified. The data support future combinatorial therapy research with liposomal irinotecan.
Rudin C, et al. RESILIENT Part 2: A Randomized, Open-label Phase 3 Study of Liposomal Irinotecan versus Topotecan in Adults with Relapsed SCLC. Presented at ELCC 2023; Abstract 161O.