SCLC highlights from 2026

By Agata Buczak 

Key ES-SCLC data from ASCO 2026

Tarlatamab shows intracranial activity in SCLC 

Tarlatamab improved intracranial outcomes compared with chemotherapy in patients with small-cell lung cancer (SCLC) and baseline brain metastases (BM), according to a post hoc analysis from the phase 3 DeLLphi‑304 study presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Giannis S. Mountzios (Henry Dunant Hospital Center, Athens, Greece) reported that median central nervous system (CNS) progression-free survival (PFS) was 6.5 months with tarlatamab compared with 4.2 months with chemotherapy (hazard ratio [HR], 0.40). Median overall survival (OS) in patients with BM at baseline was 13.9 months versus 6.8 months, respectively (HR, 0.51).

Intracranial response outcomes were higher with tarlatamab. CNS tumor shrinkage of at least 30% occurred in 56% of patients receiving tarlatamab compared with 38% with chemotherapy, while CNS complete response was observed in 15% and 5% of patients, respectively.

DeLLphi‑304 randomized 509 patients 1:1 to tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin) in the second-line setting, with 39% of patients in each arm presenting with BM at baseline. Most patients with BM had received prior CNS-directed therapy.

The safety profile in patients with BM was generally comparable between groups. Treatment-emergent adverse events of any grade occurred in 99% of patients receiving tarlatamab and 100% receiving chemotherapy. Grade 3 events occurred in 38% of patients in both groups, while grade 4 events were less frequent with tarlatamab (9% vs 40%).

The investigators concluded that tarlatamab was associated with improved intracranial efficacy, with longer CNS PFS and OS compared with chemotherapy in patients with stable, treated, and untreated asymptomatic BM.

Second-line ES-SCLC outcomes vary

Data presented at ASCO 2026 provide insights into treatment patterns, clinical outcomes, and emerging biomarker-driven strategies in the second-line extensive-stage SCLC (ES-SCLC) setting.

Catherine Rinaldi (Flatiron Health, New York, USA) presented a real-world analysis of second-line treatment patterns and outcomes following first-line chemoimmunotherapy. Outcomes varied according to platinum sensitivity, with patients with platinum-refractory disease experiencing shorter PFS and OS than those with platinum-sensitive disease.

Among patients with platinum-sensitive disease, treatment approaches included platinum rechallenge and continuation of checkpoint inhibitor (CPI) therapy; however, continuation of CPI therapy in the second-line setting was not associated with improvements in PFS or OS. These findings highlight heterogeneity in outcomes within the second-line population.

Additional real-world evidence from the EMERGE 402 study, presented by Firas Benyamine Badin (Baptist Health Medical Group, Lexington, Kentucky, USA), showed that lurbinectedin demonstrated clinical activity across a broad patient population, including those with poor prognostic features.

Outcomes differed across subgroups, with improved outcomes observed in patients with a chemotherapy-free interval of ≥90 days and those with better performance status. Despite this activity, most patients discontinued treatment, with disease progression reported as the primary reason for discontinuation.

Biomarker-driven strategies are also being explored in this setting. Jessica Ross (Memorial Sloan Kettering Cancer Center, New York, USA) presented an analysis evaluating the association between DLL3 expression and response to the bispecific T-cell engager tarlatamab.

Clinical outcomes were associated with DLL3 expression, with patients with low DLL3 expression demonstrating lower response rates and shorter PFS and OS than those with high expression. Most patients in this cohort had DLL3-high disease, with a reported response rate of 48%.

Overall, these studies describe variability in second-line outcomes in ES-SCLC and associations between DLL3 expression and clinical outcomes.

Concurrent thoracic radiotherapy fails to improve survival in ES-SCLC

Adding concurrent thoracic radiotherapy (TRT) to standard chemoimmunotherapy did not improve survival in patients with ES-SCLC, according to phase 3 data presented by Bjørn Henning Grønberg (St. Olavs Hospital and Norwegian University of Science and Technology, Norway).

This randomized phase 3 trial across hospitals in Norway, Sweden, Estonia, Iceland, and the Netherlands evaluated the addition of TRT to first-line platinum–etoposide plus durvalumab. A total of 228 patients were randomized to receive chemoimmunotherapy with or without concurrent TRT (30 Gy in 10 fractions), initiated during early treatment.

Grønberg reported that the addition of TRT “did not improve survival among patients receiving chemoimmunotherapy,” with no major differences observed across key clinical endpoints. Median OS was similar between groups (10.0 vs 11.8 months), and PFS was comparable (median 5.1 vs 5.0 months). Response rates were also similar between treatment arms.

At interim analysis, the trial was stopped early on the recommendation of the safety monitoring committee due to futility and increased toxicity in the TRT arm. There were more adverse events and treatment-related deaths in patients receiving TRT, along with a higher incidence of serious adverse events. Esophagitis was a frequent toxicity in the TRT group, including grade ≥3 events.

In this clinical setting, the addition of TRT to chemoimmunotherapy did not improve OS and was associated with increased toxicity in patients with ES-SCLC.