Real-world multi-institution analysis of tarlatamab in patients with small cell lung cancer

Tarlatamab has revolutionized the management of small cell lung cancer (SCLC) and is now a standard of care second-line therapy. Adoption of tarlatamab after FDA approval in the US has been rapid. However, real-world outcomes for patients who would not have met eligibility criteria for the clinical trials evaluating tarlatamab is not well-understood.

We designed a multicenter retrospective cohort study of three US institutions evaluating patients with SCLC who had received at least one dose of tarlatamab between 5/16/2024 and 6/15/2025. "Trial-ineligible" population was defined as patients with ECOG performance status ≥ 2, history of grade ≥ 2 pneumonitis or interstitial lung disease, untreated brain metastases, organ dysfunction, oxygen requirement or pleural effusion, history of stroke in past 12 months, or ejection fraction < 50%. Primary study outcomes were measures of efficacy including best overall response per investigator and median time on treatment and measures of toxicity including incidence and severity of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity (ICANS).

102 patients were identified. Median age was 64; patients were mostly white (92%) with a current or former tobacco use history (94%). 60 patients (59%) would have been ineligible for trial. Of patients evaluable for response (n = 80), eligible patients (n = 34) were more likely to have partial response or stable disease (70%), whereas ineligible patients were more likely to have progressive disease (57%), p = 0.047. Eligible patients had longer median time on treatment (4.8 months (95% CI 3.1-NR) vs 2.1 months (95% CI 1.6-5.6), p = 0.06. There was no difference in CRS incidence between groups (63% vs 59%, p = 0.8), but ICANS was more common in the ineligible group (33% vs 14%, p = 0.038).

Tarlatamab may be broadly applied for patients not eligible for trial enrollment, though with potential for lower efficacy.