Poor Performance Status Associated With Inferior Tarlatamab Outcomes in a Large, Multi-institution Real-World Database of Patients With 2L + ES-SCLC.

PURPOSE: Tarlatamab is approved for 2L + extensive-stage small cell lung cancer. In previously published retrospective studies, tarlatamab resulted in inferior survival compared to that observed in the DeLLphi-304 trial. To better understand real-world outcomes with tarlatamab, we examined a much larger, multi-institutional dataset.

METHODS

Utilizing the US-based, de-identified Flatiron Health Research Database, patients treated with tarlatamab between March 2024 and September 2025 were identified. Baseline characteristics, treatment history, and clinical outcomes were summarized. Median time to treatment discontinuation (mTTD), real-world progression-free survival (mPFS), and overall survival (mOS) from the start of tarlatamab were estimated via Kaplan-Meier methods. Effects of baseline patient characteristics were estimated via log-rank analysis and Cox regression.

RESULTS

Of 204 patients identified, 90 (44%) were female. Sixty-two (30%) patients were ECOG PS 0, 86 (42%) were ECOG 1, and 48 (24%) were ECOG ≥ 2. 75 (37%) received tarlatamab in 2 L, 64 (32%) in 3 L, and 65 (31%) in 4L + . mPFS was 3.8 months(m), mTTD was 2.3 m, and mOS was 11.2 m. Patient sex, race (Black vs. White), and age (<65 vs. ≥ 65 years old) were not associated with TTD, PFS, or OS. ECOG PS ≥ 2 compared to ECOG 0-1 was associated with shorter mPFS (2.1 vs. 4.5; P = .004); mTTD (1.6 vs. 2.8; P = .001) and mOS (3.2 vs. 13.4; P < .001).

CONCLUSION

In the largest retrospective analysis to date, mTTD, mPFS, and mOS in patients with intact PS (0-1) appeared similar to outcomes reported in DeLLphi-304. By contrast, ECOG PS ≥ 2 was associated with shorter TTD, PFS, and OS, which may account for inferior real-world outcomes compared to the trial. Line of therapy in our cohort was not associated with outcomes; nor was race, sex, or age.