Performance Status Predicts Real-World Outcomes With Tarlatamab in Extensive-Stage Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: This retrospective real-world study evaluated outcomes among 204 patients with extensive-stage small cell lung cancer treated with tarlatamab across multiple US institutions.
• Key Outcomes: Patients with ECOG performance status 0-1 achieved progression-free survival and overall survival similar to those reported in the phase 3 DeLLphi-304 trial. In contrast, ECOG performance status ≥2 was associated with significantly shorter treatment duration, progression-free survival, and overall survival.
• Clinical Relevance: These findings suggest that baseline performance status is a key determinant of outcomes with tarlatamab in routine clinical practice and may explain previously reported differences between real-world and clinical trial results.

Results from a real-world study demonstrated that patients with extensive-stage small cell lung cancer (ES-SCLC) and preserved performance status achieved outcomes with tarlatamab comparable to those reported in the phase 3 DeLLphi-304 trial, while patients with poorer functional status experienced substantially inferior survival. 

“In previously published retrospective studies, tarlatamab resulted in inferior survival compared to that observed in the DeLLphi-304 trial,” stated Adam Barsouk, MD, Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, and coauthors. “To better understand real world outcomes with tarlatamab, we examined a much larger, multi-institutional dataset.” 

Using the US-based Flatiron Health Research Database, investigators identified 204 patients with ES-SCLC who received tarlatamab in the second-line (37%), third-line (32%), or fourth-line or later (31%) setting. Most patients had an ECOG performance status of 0 or 1 (72%), while 24% had an ECOG performance status of ≥ 2. The primary end points were progression-free survival (PFS), time to treatment discontinuation, and overall survival (OS) from initiation of tarlatamab.

Across the overall study population, median PFS was 3.8 months, median time to treatment discontinuation was 2.3 months, and median OS was 11.2 months. 

Performance status emerged as the strongest predictor of clinical outcomes. Patients with ECOG performance status ≥2 had significantly shorter median PFS than those with ECOG performance status 0 or 1 (2.1 vs 4.5 months; P = .004), as well as shorter median time to treatment discontinuation (1.6 vs 2.8 months; P = .001) and median OS (3.2 vs 13.4 months; P < .001).

In contrast, line of therapy, age, sex, and race were not significantly associated with treatment duration, PFS, or OS. 

“This large real-world cohort of SCLC patients treated with tarlatamab exhibited efficacy mirroring that observed in pivotal clinical trial data, provided patients maintained a good performance status,” concluded Dr Barsouk et al. “Tarlatamab offers significant clinical benefit across multiple demographic subgroups and lines of therapy in ES-SCLC, but careful patient selection remains critical to maximizing benefit and minimizing harm.”

Source:

Barousk AA, Yaskolko M, Sussman JH, et al. Poor performance status associated with inferior tarlatamab outcomes in a large, multi-institution real world database of patients with 2L+ ES-SCLC. Clin Lung Cancer. Published online: July 2, 2026. doi: 10.1016/j.cllc.2026.07.001