Matching-Adjusted Indirect Comparison of Tarlatamab for Patients with Platinum-Refractory or Platinum-Resistant Extensive-Stage Small-Cell Lung Cancer.

Authors

Franziska Dirnberger, Sachin Patel, Devon J Boyne, Zhiyi Lan, Jenny Uyei, Jessie Wang, Seoyoon Cho, Lucy DeCosta, Ian M Bridges, Umit Tapan

Published in

Advances in therapy. Jun 30, 2026. Epub Jun 30, 2026.

Abstract

Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive cancer that is traditionally associated with poor survival outcomes, particularly among individuals with platinum-refractory or platinum-resistant disease. In the phase 3 DeLLphi-304 trial (NCT05740566), tarlatamab showed significant clinical benefit compared with single-agent chemotherapies (topotecan, lurbinectedin, or amrubicin) as second-line (2L) therapy for ES-SCLC. Paclitaxel and a combination of cyclophosphamide, doxorubicin, and vincristine (CAV) are alternative 2L treatments for platinum-refractory or platinum-resistant ES-SCLC that were not evaluated in the DeLLphi-304 trial. To address the lack of head-to-head evidence, unanchored matching-adjusted indirect comparisons (MAICs) were conducted to compare the efficacy of tarlatamab versus paclitaxel and CAV.
The analyses leveraged individual-level patient data from DeLLphi-304 (tarlatamab) and published aggregate-level data from Owonikoko 2020 (NCT02038647; paclitaxel) and GFPC 0501 (NCT00418743; CAV). Analyses were restricted based on chemotherapy-free interval (CFI) to align with the eligibility criteria of Owonikoko 2020 (CFI < 180 days) and GFPC 0501 (CFI < 90 days). Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR). Unanchored MAIC was used to estimate the relative treatment effect after adjusting for baseline imbalances. Measures of effect included hazard ratios (HRs) and odds ratios (ORs).
After MAIC reweighting, tarlatamab was associated with longer OS versus paclitaxel [HR (95% CI): 0.35 (0.23, 0.52), p < 0.001] and CAV [HR: 0.48 (0.32, 0.70), p < 0.001]. Tarlatamab was also associated with improved PFS, ORR and DCR relative to paclitaxel (p < 0.05). There were no significant differences between tarlatamab and CAV with respect to PFS, ORR, or DCR (p > 0.05).
These results suggest that tarlatamab may increase survival relative to paclitaxel and CAV among individuals with platinum-refractory or platinum-resistant ES-SCLC in the 2L setting. These findings are subject to residual confounding and should be interpreted with caution.
DeLLphi-304 ClinicalTrials.gov identifier, NCT05740566.

PMID:
42377743
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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