Network Meta-Analysis NMA of Clinical Effectiveness of Second-Line (2L+) Treatments in Extensive-Stage Small Cell Lung Cancer (ES-SCLC)
Author(s)
Fiona Blackhall, BSc, MBChB, FRCP, PhD, CCST1, Jessie Wang, DSc2, Rumbi Takundwa, BA, MSc3, Youfei Yu, BA, MS, PhD2, Hongbo Yang, BA, MA, PhD4, Xinglei Chai, PhD4, Yuehan Zhang, BS, ScM, PhD4, Erik Anderson, MD, PhD2, Pastel Malaika, PhD2.
1The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Amgen Inc, Thousand Oaks, CA, USA, 3Amgen Ltd, Uxbridge, United Kingdom, 4Analysis Group Inc, Boston, MA, USA.
1The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Amgen Inc, Thousand Oaks, CA, USA, 3Amgen Ltd, Uxbridge, United Kingdom, 4Analysis Group Inc, Boston, MA, USA.
OBJECTIVES: Treatment options after recurrence of ES-SCLC typically depend on patients’ platinum-sensitivity status but are generally associated with poor outcomes. DeLLphi-304, an ongoing phase III randomized controlled trial (RCT), showed that tarlatamab offers considerable clinical benefit in head-to-head comparisons versus chemotherapies (topotecan, amrubicin, or lurbinectedin). An NMA was conducted to indirectly compare tarlatamab with existing 2L treatments, including those not evaluated in DeLLphi-304.
METHODS: Bayesian NMAs using fixed effects models were used to compare overall survival (OS) and progression-free survival (PFS) among treatments in the overall 2L population (tarlatamab, topotecan, cyclophosphamide + doxorubicin + vincristine [CAV], amrubicin, and irinotecan-based regimens) and the platinum-sensitive (defined as chemotherapy-free interval ≥ 90 days) subgroup (tarlatamab, topotecan, platinum rechallenge, amrubicin, and liposomal irinotecan).
RESULTS: In the overall 2L population, tarlatamab demonstrated significant improvements in OS compared to all comparators, with hazard ratios (HRs) ranging from 0.50 (95% credible interval [CrI]: 0.35, 0.70) versus liposomal irinotecan to 0.62 (0.45, 0.87) versus amrubicin. PFS was trending in favor of tarlatamab with HRs ranging from 0.68 (0.49, 0.93) versus irinotecan to 0.94 (0.71, 1.25) versus amrubicin. A similar trend was observed in the NMA of the platinum-sensitive subgroup, where OS for tarlatamab was significantly better than liposomal irinotecan (HR: 0.51 [0.31, 0.84]), platinum rechallenge (0.56 [0.37, 0.86]), topotecan (0.59 [0.40, 0.87]), and amrubicin (0.63 [0.40, 0.98]). No difference was shown in PFS between tarlatamab and comparators with HRs ranging from 0.79 (0.58, 1.05) versus topotecan to 1.19 (0.80, 1.76) versus platinum rechallenge.
CONCLUSIONS: Tarlatamab demonstrated significantly improved OS compared to existing treatments in patients with previously treated ES-SCLC, irrespective of platinum-sensitivity status, supporting its potential to be the new standard of care.
METHODS: Bayesian NMAs using fixed effects models were used to compare overall survival (OS) and progression-free survival (PFS) among treatments in the overall 2L population (tarlatamab, topotecan, cyclophosphamide + doxorubicin + vincristine [CAV], amrubicin, and irinotecan-based regimens) and the platinum-sensitive (defined as chemotherapy-free interval ≥ 90 days) subgroup (tarlatamab, topotecan, platinum rechallenge, amrubicin, and liposomal irinotecan).
RESULTS: In the overall 2L population, tarlatamab demonstrated significant improvements in OS compared to all comparators, with hazard ratios (HRs) ranging from 0.50 (95% credible interval [CrI]: 0.35, 0.70) versus liposomal irinotecan to 0.62 (0.45, 0.87) versus amrubicin. PFS was trending in favor of tarlatamab with HRs ranging from 0.68 (0.49, 0.93) versus irinotecan to 0.94 (0.71, 1.25) versus amrubicin. A similar trend was observed in the NMA of the platinum-sensitive subgroup, where OS for tarlatamab was significantly better than liposomal irinotecan (HR: 0.51 [0.31, 0.84]), platinum rechallenge (0.56 [0.37, 0.86]), topotecan (0.59 [0.40, 0.87]), and amrubicin (0.63 [0.40, 0.98]). No difference was shown in PFS between tarlatamab and comparators with HRs ranging from 0.79 (0.58, 1.05) versus topotecan to 1.19 (0.80, 1.76) versus platinum rechallenge.
CONCLUSIONS: Tarlatamab demonstrated significantly improved OS compared to existing treatments in patients with previously treated ES-SCLC, irrespective of platinum-sensitivity status, supporting its potential to be the new standard of care.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO169
Topic
Clinical Outcomes, Health Technology Assessment, Methodological & Statistical Research
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology