Dr Liu on Building on the ADRIATIC Regimen in Limited-Stage Small Cell Lung Cancer

“We know that we cure some [patients with limited-stage small cell lung cancer], but not nearly enough. We have better drugs, we have newer agents, and how to incorporate them into [the] earlier-stage setting will be the next challenge over these next few years.”

Stephen V. Liu, MD, associate professor of medicine at Georgetown University, division chief of hematology and oncology at MedStar Georgetown University Hospital, and director of thoracic oncology and head of developmental therapeutics at Georgetown Lombardi Comprehensive Cancer Center, discussed survival data from the phase 3 ADRIATIC trial (NCT03703297) evaluating consolidation durvalumab (Imfinzi) after chemoradiotherapy in limited-stage small cell lung cancer (SCLC), and how agents such as the DLL3-targeted bispecific T-cell engager tarlatamab-dlle (Imdelltra) might build on that benefit.

Consolidation durvalumab after concurrent chemoradiotherapy became the standard of care in limited-stage SCLC based on data from the ADRIATIC trial, which showed a median overall survival (OS) of 55.9 months (95% CI, 37.3-not reached) with durvalumab vs 33.4 months (95% CI, 25.5-39.9) with placebo (HR, 0.73; 98.321% CI, 0.54-0.98; P = .0104) and a median progression-free survival (PFS) of 16.6 months (95% CI, 10.2-28.2) vs 9.2 months (95% CI, 7.4 to 12.9) among 730 patients (HR, 0.76; 97.195% CI, 0.59-0.98; P = .0161), Liu noted, translating to an improvement in median OS of nearly 2 years.

According to Liu, tarlatamab, a DLL3 x CD3 bispecific approved for extensive-stage SCLC, has generated interest as a way to build on durvalumab consolidation, though he raised questions around patient selection, access, delivery, and treatment duration in the limited-stage setting. The phase 3 DeLLphi-306 trial (NCT06117774) is testing tarlatamab against placebo after chemoradiotherapy in limited-stage SCLC, but Liu noted it was designed before the ADRIATIC data emerged and so lacks a durvalumab comparator. He said a more clinically relevant question is whether tarlatamab can be added to durvalumab, or whether patients can be selected for one strategy over the other, an approach now being tested in a newly launched trial (NCT07637513) comparing tarlatamab plus durvalumab with durvalumab alone. Liu called this an area with many interesting trials that should meaningfully reshape the limited-stage SCLC landscape over the next few years.