Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer
In brief
Tarlatamab-durvalumab adds 8 months to median survival in small-cell lung cancer
In a phase 3 trial, patients whose cancer had not progressed after initial chemoimmunotherapy lived a median 21.1 months with tarlatamab plus durvalumab, versus 12.7 months with durvalumab alone. Progression-free survival also improved, but serious side effects were more common and cytokine release syndrome affected nearly half of combination-treated patients; longer follow-up will clarify durability.
- Journal
- The New England journal of medicine (Q1)
- Published
- 24 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Maurice Pérol, Tatsuya Yoshida, Myung-Ju Ahn, Carl M Gay, Martin Schuler, Haifeng Liu, et al.
- PMID
- 42929702
- DOI
- 10.1056/NEJMoa2609482
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 27 October 2026): Randomized phase III maintenance bispecific-antibody and immunotherapy trial
Abstract
BACKGROUND: Patients with extensive-stage small-cell lung cancer have poor outcomes, with a median overall survival of approximately 12 to 13 months. Tarlatamab (a bispecific T-cell engager targeting delta-like ligand 3 [DLL3] and CD3) was previously shown to improve survival as second-line therapy. Whether adding tarlatamab to durvalumab (an anti-programmed death ligand 1 agent) after initial chemoimmunotherapy could significantly improve survival in the context of maintenance therapy after first remission has been unclear. METHODS: In this phase 3, international, open-label, randomized trial, we compared tarlatamab-durvalumab with durvalumab as first-line maintenance therapy in patients with extensive-stage small-cell lung cancer without progression after initial chemoimmunotherapy. Overall survival and progression-free survival were assessed from randomization at the start of maintenance therapy as the primary and key secondary end points, respectively. Results of the prespecified interim analysis (data-cutoff date, July 7, 2026) are reported here. RESULTS: A total of 563 patients were randomly assigned to receive tarlatamab-durvalumab (282 patients) or durvalumab (281 patients). At a median follow-up of 15.9 months in the tarlatamab-durvalumab group and 16.1 months in the durvalumab group, the estimated median overall survival was 21.1 months (95% confidence interval [CI], 20.8 to could not be estimated) with tarlatamab-durvalumab and 12.7 months (95% CI, 11.2 to 14.8) with durvalumab (hazard ratio for death, 0.42; 95% CI, 0.32 to 0.54; P<0.001). The median progression-free survival was 7.4 months (95% CI, 5.6 to 9.1) with tarlatamab-durvalumab and 1.9 months (95% CI, 1.9 to 2.0) with durvalumab (hazard ratio for disease progression or death, 0.34; 95% CI, 0.28 to 0.42; P<0.001). Adverse events of grade 3 or higher occurred in 46.8% of the patients who received tarlatamab-durvalumab and in 40.6% of those who received durvalumab alone. Cytokine release syndrome, mainly of grade 1 or 2, was seen in nearly half the patients receiving tarlatamab-durvalumab. CONCLUSIONS: Tarlatamab-durvalumab maintenance therapy resulted in significantly longer overall survival and progression-free survival than durvalumab alone among patients with extensive-stage small-cell lung cancer. (Funded by Amgen and AstraZeneca; DeLLphi-305 ClinicalTrials.gov number, NCT06211036.).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.