Most patients with SCLC relapse within 1 year of receiving first-line (1L) platinum therapy; second-line treatment options are limited. We report the results of RESILIENT, a randomized, open-label phase III trial of liposomal irinotecan versus topotecan in patients with SCLC that had progressed on or after 1L platinum-based therapy.
Eligible patients with histologically or cytologically confirmed SCLC and radiologically confirmed disease progression despite 1L platinum-based chemotherapy were randomized (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).
Overall, 461 patients (median [range] age, 62.0 [28.0–82.0] years; 67.9% men; 74.2% ECOG performance status 1) were randomized to receive liposomal irinotecan (n = 229) or topotecan (n = 232); median follow-up was 18.4 months. Median OS and PFS were 7.9 months and 4.0 months, respectively, with liposomal irinotecan versus 8.3 months and 3.3 months with topotecan. Hazard ratios (HRs) and 95% confidence intervals (CIs) for death, and for disease progression or death, are shown in the
| Liposomal irinotecan | Topotecan | |
|---|---|---|
| OS, median (95% CI) months | 7.9 (6.9–9.2) | 8.3 (7.3–9.1) |
| HR for death (95% CI) | 1.11 (0.90–1.37), p = 0.3094 | |
| PFS per BICR, median (95% CI) months | 4.0 (3.0–4.2) | 3.3 (2.8–4.1) |
| HR for disease progression or death (95% CI) | 0.96 (0.77–1.20), nominal p = 0.7053 | |
| ORR per BICR, % (95% CI) | 44.1 (37.6–50.8) | 21.6 (16.4–27.4) |
| Patients with a grade >3 treatment-related TEAE, % | 42.0 | 83.4 |
| Grade >3 treatment-related TEAEs occurring in >10% of patients, % | ||
| Diarrhea | 13.7 | 1.3 |
| Neutropenia | 8.0 | 51.6 |
| Neutrophil count decreased | 4.4 | 17.5 |
| Leukopenia | 4.0 | 29.1 |
| White blood cell count decreased | 4.0 | 10.8 |
| Anemia | 2.7 | 30.9 |
| Platelet count decreased | 1.3 | 17.5 |
| Thrombocytopenia | 0.4 | 29.1 |
The primary endpoint of OS for was not met for liposomal irinotecan versus topotecan; however, a doubling of ORR was observed. The safety profile of liposomal irinotecan was consistent with its known safety profile and no new safety concerns emerged.
NCT03088813.
Medical writing support was provided by Emma Bolton, PhD, of Oxford PharmaGenesis, Oxford, UK which was funded by Ipsen in accordance with Good Publication Practice 2022 guidelines.
Ipsen.
Ipsen.
A. Dowlati: Financial Interests, Institutional, Other, Consultancy: AbbVie/Stemcentrx, ARIAD Pharmaceuticals; Financial Interests, Institutional, Research Grant: Amgen, Bristol Myers Squibb, Eli Lilly/ImClone Systems, EMD Serono, MedImmune; Financial Interests, Personal, Research Grant: OncoMed. Y. Chen: Financial Interests, Personal, Invited Speaker: Array BioPharma, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, Guardant Health, Heron Therapeutics, Merck, Novartis, Pfizer, Takeda; Financial Interests, Personal, Other, Consultant: Array BioPharma, AstraZeneca, Bristol Myers Squibb, Genentech, Heron Therapeutics, Novartis, Pfizer, Takeda; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Funding: Bristol Myers Squibb, Guardant Health, Helsinn, Ipsen, Roche; Non-Financial Interests, Personal, Expert Testimony: AstraZeneca, Takeda; Financial Interests, Institutional, Other, Clinical trials: AstraZeneca; Financial Interests, Personal, Other, Clinical trials: Bristol Myers Squibb, Ipsen, Roche. A.F. Navarro Mendivil: Other, Institutional, Advisory Board: Boehringer Ingelheim, Oryzon Genomics, Amgen, Hengenix Biotech, MedSIR; Other, Institutional, Speaker's Bureau: Roche, AstraZeneca, BMS, Pfizer, Takeda. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis, AstraZeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Personal, Member: ASCO.
G. Stojanovic: Other, Institutional, Invited Speaker: MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca. Z.G. Andric: Financial Interests, Personal, Invited Speaker: MSD, Roche, AstraZeneca, Novartis, Merck-D. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). H. Chen: Financial Interests, Personal and Institutional, Other, Employee: Ipsen. L. Zhang: Financial Interests, Institutional, Full or part-time Employment: Ipsen. S. Yeung: Financial Interests, Institutional, Full or part-time Employment: Ipsen. F.M. Benzaghou: Financial Interests, Institutional, Full or part-time Employment: Ipsen. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AstraZeneca, Eli Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Eli Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. P.A. Bunn: Financial Interests, Personal, Other, Consultancy: AstraZeneca, Ascentage, C-Stone, Genentech, Imidex, Ipsen, Celgene, Merck, Viecure. All other authors have declared no conflicts of interest.