Tarlatamab combination extends survival during lung-cancer maintenance treatment
The phase III DeLLphi-305 trial reported longer survival with tarlatamab plus durvalumab during first-line maintenance for extensive-stage small cell lung cancer. Patients entered after their disease had not progressed on initial treatment. The interim analysis also found a longer period without progression. Adverse effects included immune-related reactions, and longer-term follow-up continues.
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Maintenance treatment followed the initial cancer therapy
Adding tarlatamab to durvalumab prolonged survival during first-line maintenance for extensive-stage small cell lung cancer in the phase III DeLLphi-305 trial. The comparison involved patients whose disease had not progressed after initial durvalumab, platinum and etoposide treatment. Tarlatamab with durvalumab was compared with durvalumab alone. Both overall survival and the period without disease progression improved in the interim analysis. CancerNetwork reported the same maintenance-treatment result. Dana-Farber Cancer Institute, the US cancer research and treatment centre, announced the findings on 24 October and said they were simultaneously published in the New England Journal of Medicine. The results concern this defined treatment sequence.[1], [2]
The combination directs immunity through different routes
Tarlatamab brings immune cells close to cancer cells by binding targets on both. It attaches to CD3 on T cells, an immune-cell type, and DLL3 on small cell lung cancer cells. Durvalumab works through an immune checkpoint instead. The clinical rationale for testing the combination during maintenance includes the disease’s rapid progression: some patients never reach a second treatment line. The announcement described benefits in subgroups with brain or liver metastases. The setting differs from the later-line use for which tarlatamab already has approval. That existing approval and the proposed earlier maintenance use concern different stages in the treatment pathway, with ongoing follow-up of the trial population. The institute’s announcement described the subgroup findings as part of the trial result, without implying that every individual responded identically.[1]
Immune reactions remained part of the safety assessment
Adverse effects included reduced neutrophil counts, appetite loss, fatigue and weight loss. Neutrophils are infection-fighting white blood cells. Cytokine release syndrome, an immune reaction, also occurred and was most commonly low grade. These effects accompany the reported efficacy findings in the interim analysis. Jacob Sands, associate chief of Dana-Farber’s Lowe Center for Thoracic Oncology, presented the results at the European Society for Medical Oncology congress in Madrid. Amgen sponsors the trial, while AstraZeneca provides partial funding and durvalumab. The institute described this as the first phase III overall-survival benefit for a bispecific T-cell engager in the first-line maintenance setting. Longer-term observation continues in the studied clinical population.[1]
