Real-World Analysis Identifies Performance Status as a Key Predictor of Outcomes With Tarlatamab in Extensive-Stage Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: This retrospective, multi-institutional real-world study evaluated patients with previously treated extensive-stage small cell lung cancer who received tarlatamab between March 2024 and September 2025 using the Flatiron Health Research Database.
• Key Outcomes: Median progression-free survival, time to treatment discontinuation, and overall survival were 3.8, 2.3, and 11.2 months, respectively. Patients with ECOG performance status ≥2 had significantly poorer outcomes than those with ECOG performance status 0-1, whereas age, sex, race, and line of therapy were not associated with outcomes.
• Clinical Relevance: These real-world findings suggest that tarlatamab can achieve outcomes comparable to those observed in clinical trials among appropriately selected patients with good performance status while underscoring the importance of ECOG performance status when considering treatment.

Results from the largest real-world analysis of tarlatamab to date demonstrated that baseline performance status was a major determinant of clinical outcomes in patients with previously treated extensive-stage small cell lung cancer, whereas age, sex, race, and line of therapy did not significantly influence survival.

"Tarlatamab is approved for [second-line and later] extensive-stage small cell lung cancer," stated Adam Barsouk, MD, Abramson Cancer Center, Philadelphia, Pennsylvania, and coauthors. “With increasing use of tarlatamab and given its unique toxicities and burden on resources with the need to hospitalize patients for observation during the initial infusions, it is important to assess real-world efficacy on a larger scale.” 

In this retrospective cohort study, investigators analyzed data from the US-based Flatiron Health Research Database, identifying 204 adults who initiated tarlatamab between March 2024 and September 2025 after receiving at least 1 prior line of systemic therapy. Primary end points included overall survival (OS), progression-free survival (PFS), and time to treatment discontinuation. Survival outcomes were estimated using Kaplan-Meier methods, and prognostic factors were evaluated with log-rank testing and Cox regression analyses.

At a median follow-up of 15.4 months, median PFS was 3.8 months, median time to treatment discontinuation was 2.3 months, and median OS was 11.2 months.

Performance status was strongly associated with clinical outcomes. Patients with an ECOG performance status of 0-1 achieved a median OS of 13.4 months compared with 3.2 months among those with an ECOG performance status ≥2 (hazard ratio [HR], 2.65; P = .002). Patients with ECOG performance status ≥2 also experienced significantly shorter median PFS (2.1 vs 4.5 months; P = .004) and median time to treatment discontinuation (1.6 vs 2.8 months; P = .001). On multivariable analysis, ECOG performance status ≥2 remained independently associated with worse OS (HR, 3.09; 95% CI, 1.64-5.83; P < .001), PFS (HR, 3.06; P < .001), and time to treatment discontinuation (HR, 1.84; P = .007).

By contrast, investigators observed no significant associations between age, sex, race, or treatment line and clinical outcomes. Patients treated in the second-line setting achieved a median PFS of 5.3 months and median OS of 12.2 months, compared with 3.4 months and 8.1 months, respectively, among those treated in the third-line setting or beyond; however, these differences were not statistically significant. Similarly, survival outcomes were comparable across age, sex, and racial subgroups.

“We found that patients with intact [performance status] achieved similar outcomes to the DeLLphi trials, providing critical context to earlier, single-institution reports suggesting underperformance of the drug outside of clinical trials,” concluded Dr Barsouk et al. “Tarlatamab offers significant clinical benefit across multiple demographic subgroups and lines of therapy, but careful patient selection remains critical to maximizing benefit and minimizing harm.”

Source: 

Barsouk 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