Real-world efficacy and safety of tarlatamab in extensive-stage small-cell lung cancer: A single-center retrospective study at university of Missouri.

Abstract

e20150 Background: Tarlatamab is a standard second-line treatment for extensive-stage small cell lung cancer (ES-SCLC); however, real-world outcome data remain limited. Methods: We conducted a single-center retrospective study at Ellis Fischel Cancer Center, University of Missouri. Adults with ES-SCLC who received prior platinum-based therapy and ≥1 full dose of tarlatamab between May 1, 2024, and December 1, 2025, were included. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), real-world progression-free survival (rwPFS), overall survival (OS), and intracranial PFS (IC-PFS). Safety endpoints included cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and other treatment-related adverse events (TRAEs). Exploratory analyses included subgroup DCRs and post-tarlatamab treatment patterns. Results: Twenty patients were included. Median follow-up was 193 days, and median age was 63 years. At baseline, 70% had brain metastases, 35% had liver metastases, and 30% had received ≥3 prior lines; 30% were platinum-sensitive, and 35% had prior lurbinectedin. The ORR was 30%, and DCR was 40%. Median rwPFS was 90 days (95% CI, 66–NE); median OS was 396 days (95% CI, 113–NE); and median IC-PFS was 71 days (95% CI, 62–NE). Median IC-PFS was 86 days (95% CI, 53–NE) in patients without baseline brain metastases and 71 days (95% CI, 62–NE) in those with baseline brain metastases. CRS occurred in 20% (all grade 1–2), and ICANS in 10% (one grade 1, one grade 3), with median onset times of 12 and 9.5 hours. Steroids, tocilizumab, and ICU admission were required in 25%, 10%, and 10%, respectively. Median cycle 1 hospital stay was 2 days. Other TRAEs included anemia (5%), lymphopenia (10%), hypoalbuminemia (10%), dysgeusia (20%), and one grade ≥3 transaminitis. Subgroup DCRs were 42.9% vs 38.5% (platinum-sensitive vs -resistant), 20.0% vs 46.7% (bulky vs non-bulky), 42.9% vs 33.3% (brain metastases vs none), 28.6% vs 46.2% (liver metastases vs none), and 20.0% vs 46.7% (CRS/ICANS vs none). Of 11 patients who progressed on tarlatamab, only 3 received subsequent systemic therapy (lurbinectedin, n = 2; platinum, n = 1), with treatment durations of 43–104 days. Conclusions: In this single-center real-world cohort, tarlatamab demonstrated safety and efficacy generally consistent with the DeLLphi-304 trial, with lower CRS rates. Few patients received subsequent systemic therapy, highlighting limited post-tarlatamab options. Exploratory subgroup findings suggest potential heterogeneity in treatment response by metastatic pattern and treatment-related toxicity, warranting further investigation. Lastly, most of our patients are suburban and rural patients, emphasizing collaboration with local community oncologists to provide access to tarlatamab in rural settings.