Dr Alder on Treatment Beyond Progression With Tarlatamab in SCLC

Local consolidation, especially SRS to the brain, can really improve outcomes and continue a patient on a drug that's working exceptionally well everywhere else, except for the brain, which does seem like a site where progression can be an issue.

In an interview with OncLive at the IASLC 2026 World Conference on Lung Cancer (WCLC) in Seoul, Laura Alder, MD, assistant professor of medicine, Division of Medical Oncology, Duke University School of Medicine, discussed a two-center, real-world analysis of treatment beyond progression with tarlatamab (Imdelltra) in small cell lung cancer (SCLC).

At WCLC 2026, Alder and colleagues presented a retrospective analysis of 79 patients with SCLC treated with tarlatamab, a DLL3-directed bispecific T-cell engager, at 2 academic centers between June 2024 and December 2025. Oligoprogression was defined as ≤5 progressive or new lesions in ≤2 organs at first progression; progression was assessed by the treating physician rather than by strict RECIST criteria.

Forty-six patients (58%) progressed, 22 of them (48%) with oligoprogressive disease, and 14 patients (18%) continued tarlatamab beyond progression: 7 with oligoprogressive and 7 with non-oligoprogressive disease. Among the 7 oligoprogressive patients treated beyond progression, the CNS was the site of first progression in 6 (86%), and 6 of 7 received local consolidative stereotactic radiosurgery (SRS) to the brain, with 1 also receiving spinal radiation.

Median PFS1 was 140 days and median PFS2 was 69 days in that group, versus 48 and 24 days in the non-oligoprogressive group, in which only 1 patient received local therapy, with whole-brain radiation.

Median overall survival (OS) was 254 days in oligoprogressive patients treated beyond progression versus 69 days in non-oligoprogressive patients treated beyond progression, 116 days in progressors who did not continue, and 119 days in the overall cohort.

Extracranial disease control was 100% in the oligoprogressive group despite CNS progression, versus 33% in the non-oligoprogressive group.

Alder said tarlatamab produces durable responses but also atypical patterns of progression, sometimes limited to a single site or organ, and isolated CNS progression is common. Drawing on the non–small cell lung cancer literature and recent frontline extensive-stage SCLC data, she said local consolidation, particularly SRS to the brain, can allow a patient to continue a drug that is controlling disease elsewhere.

The decision to continue, she said, reflected a mix of factors: how much the disease was progressing, how amenable the sites were to radiation, and whether the patient had demonstrated clinical benefit on tarlatamab.

Given the survival benefit established with the agent, she favors giving patients a few cycles to establish that tarlatamab is working before adding radiation. Disease biology over time, she said, reveals how well tarlatamab is controlling the disease overall.

A few patients progressed again within the next 1 or 2 scans, but many derived multiple months of benefit after local consolidation, Alder said.

Because the analysis was retrospective, Alder acknowledged selection bias in who received radiation, and she called for a prospective trial limited to oligoprogressive disease that randomizes patients to local consolidation with SRS or stereotactic body radiotherapy versus switching systemic therapy.

Alder noted that she avoids whole-brain radiation whenever possible. The question is particularly relevant now that the phase 3 DeLLphi-305 trial has reported a positive OS result for tarlatamab plus durvalumab (Imfinzi) as first-line maintenance in extensive-stage SCLC.