Adding Tarlatamab to Durvalumab Maintenance Lifted Median Survival to 21.1 Months in Small Cell Lung Cancer

Small cell lung cancer is among the hardest cancers to treat, and for years the progress in its extensive stage has been measured in weeks. A phase 3 trial presented at the ESMO Congress in Madrid now reports a much larger gap: patients who added a drug called tarlatamab to standard maintenance therapy lived a median of 21.1 months, against 12.7 months with the standard drug alone.

The study, DeLLphi-305, was presented in a Presidential Symposium and published at the same time in The New England Journal of Medicine; the results were released on 24 October, according to AstraZeneca's results release. It is an interim analysis, and the company, which makes the standard drug durvalumab (Imfinzi), is a source with a stake in the outcome.

What did the DeLLphi-305 trial test?

The trial enrolled 563 people with extensive-stage small cell lung cancer whose disease had not progressed after initial chemotherapy plus durvalumab. They were randomised one to one to continue durvalumab alone or to add tarlatamab, a DLL3-targeting bispecific T-cell engager that links a patient's immune cells to the tumour. OncoDaily's summary lists 175 sites in 29 countries. Patients with treated or untreated brain metastases that caused no symptoms could take part.

How much longer did patients live?

Median overall survival was 21.1 months with the combination and 12.7 months with durvalumab alone, a hazard ratio of 0.42 (95 percent confidence interval 0.32 to 0.54), which is the 58 percent reduction in the risk of death that the headline refers to. At 12 months, 79 percent of the combination group were alive versus 53 percent. Median progression-free survival was 7.4 months versus 1.9 months. The benefit was consistent across subgroups, including people with brain or liver metastases, though the subgroups were not individually powered.

What are the side effects?

Tarlatamab engages the immune system, and the trial shows it. Cytokine release syndrome, a flu-like inflammatory reaction, occurred in 49.6 percent of the combination group, mostly grade 1 or 2, with one grade 3 case and none graver, OncoDaily reports. Immune effector cell-associated neurotoxicity appeared in 1.1 percent. Grade 3 or 4 treatment-related adverse events were seen in 20.9 percent of the combination group and 10.8 percent of the durvalumab-only group, per AstraZeneca. About 5.7 percent stopped tarlatamab because of side effects, and no treatment-related deaths were reported. Nearly half of treated patients had altered taste, mostly mild.

What are the limits of the result?

Survival was measured from the start of maintenance, not from diagnosis, so the 21.1 months should not be set beside figures from first-line trials, the investigators caution. People whose cancer progressed rapidly during induction were excluded. The trial also predates the newer maintenance option of lurbinectedin plus atezolizumab, so it does not show whether tarlatamab beats it. No regulatory approval for the combination is mentioned. This was one of several cancer results from the meeting, alongside the melanoma vaccine data we reported on Sunday.

This article is reporting on a clinical trial, not medical advice. Decisions about cancer treatment, including whether any drug is suitable and what risks are acceptable, belong with an oncologist who knows the patient's history. Longer follow-up and regulatory review will show how durable the gain is and who should receive it.