Adding Tarlatamab to Durvalumab Maintenance Cut the Risk of Death 58 Percent in Extensive-Stage Small Cell Lung Cancer
Median survival was 21.1 versus 12.7 months in DeLLphi-305. Half of patients had cytokine release syndrome, and the use is not yet approved.
Adding tarlatamab-dlle (Imdelltra) to durvalumab (Imfinzi) maintenance cut the risk of death 58 percent versus durvalumab alone in extensive-stage small cell lung cancer in the phase 3 DeLLphi-305 trial, presented Oct. 24 at the ESMO Congress.
Jacob Sands, M.D., of Dana-Farber Cancer Institute presented the interim overall survival analysis (LBA3) in the European Society for Medical Oncology's Presidential Symposium, and the results were published simultaneously in the New England Journal of Medicine, according to AstraZeneca's Oct. 24 announcement. Amgen had disclosed only that the trial met its primary endpoint in a Sept. 8 release, without hazard ratios or medians. Tarlatamab, Amgen's DLL3-directed bispecific T-cell engager, is approved in the United States for extensive-stage disease that has progressed on or after platinum-based chemotherapy; first-line maintenance use is investigational, Amgen says.
Who was in the trial?
DeLLphi-305 enrolled patients after first-line treatment, not at diagnosis. The open-label trial randomized 563 patients whose disease had not progressed after induction with durvalumab, platinum and etoposide to tarlatamab 10 mg every two weeks plus durvalumab 1,500 mg every four weeks (n=282) or durvalumab alone (n=281), until progression or unacceptable toxicity, Targeted Oncology reported. Patients with treated or untreated asymptomatic brain metastases were eligible, AstraZeneca said. Overall survival was the primary endpoint.
What were the results?
At the interim analysis, with about 16 months of median follow-up and 61 percent of planned events, median overall survival was 21.1 months with the combination versus 12.7 months with durvalumab alone (HR 0.42; 95% CI, 0.32 to 0.54; P<.001). Twelve-month survival was 79 versus 53 percent. Median progression-free survival was 7.4 versus 1.9 months (HR 0.34; 95% CI, 0.28 to 0.42), and the confirmed response rate was 26.4 versus 4.1 percent.
By The Script Pad's arithmetic, the 12-month rates imply about 26 more patients alive at one year per 100 treated, roughly one for every four. Two caveats shape that number. Survival is measured from randomization after induction, so these medians cannot be compared with first-line trials that start the clock at diagnosis. And this is an interim analysis of an open-label trial, though overall survival is the endpoint least affected by open-label bias. In the presentation, Sands noted that response rate has limited meaning in maintenance, since patients enter after benefiting from induction, OncLive reported.
The survival gain is large, but it comes with a T-cell engager's monitoring burden, and it applies only to patients who reach maintenance without progression.
What about safety?
Treatment-related grade 3 or higher adverse events occurred in 20.9 versus 10.8 percent, and discontinuation for adverse events was similar, 5.7 versus 5.8 percent. Cytokine release syndrome occurred in 49.6 percent of patients on the combination, mostly low grade: 7.4 percent grade 2 and a single grade 3 event, with no grade 4 or fatal cases. About one in five patients received corticosteroids and 3.9 percent tocilizumab. Immune effector cell-associated neurotoxicity syndrome occurred in 1.1 percent, none grade 3 or higher, OncLive reported. Tarlatamab's U.S. label carries a boxed warning for cytokine release syndrome and neurologic toxicity, including ICANS, and requires step-up dosing.
What it means in clinic
Sands said the outcomes support the combination as a new standard of care for first-line maintenance, but there is no U.S. label for that use yet; Amgen said it will share the data with regulators. Practices that treat small cell lung cancer can prepare now. If approved, the combination would bring tarlatamab, with its on-site monitoring after the first doses, to patients finishing induction rather than only those who have progressed, which affects chair time, after-hours coverage and the CRS and ICANS protocols that infusion staff and emergency departments follow. Programs that already give tarlatamab should review those pathways. For other overall survival results from the same congress, see Krascendo 1 in KRAS G12C lung cancer and INTerpath-001 in melanoma.
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This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
