Evaluation of atezolizumab, durvalumab, lurbinectedin, and tarlatamab in high-grade extrapulmonary neuroendocrine carcinoma: A multicenter retrospective comparative analysis.

e20115 Background: Small cell lung cancer (SCLC) is the most common high-grade neuroendocrine neoplasm (NEN). SCLC is associated with poor survival due to treatment resistance, though in the past decade new therapies such as atezolizumab, durvalumab, lurbinectedin, and tarlatamab have shown improved outcomes. While SCLC has seen an influx of new therapies, other rarer high-grade NENs have not been studied prospectively. Treatment is still routinely extrapolated from SCLC, though limited data remains for these patients. This study aimed to evaluate atezolizumab, durvalumab, lurbinectedin, and tarlatamab regimens in patients with high-grade NENs. Methods: This retrospective study evaluated patients treated with durvalumab, atezolizumab, and lurbinectedin from 2018–2025 at the University of Kansas, and patients treated with tarlatamab from 9 cancer centers in the DLL3 PanTUMOR database. Any high-grade NEN other than SCLC was included. Key endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: A total of 54 patients were included: 24 received platinum-based therapy plus atezolizumab, 7 received platinum-based therapy plus durvalumab, 19 received lurbinectedin, and 25 received tarlatamab. Median OS with platinum-based chemotherapy and durvalumab or atezolizumab was 14.29 and 13.57 months, respectively. The ORR of tarlatamab and lurbinectedin were 47.6% and 52.6%. In 15 patients with DLL3-positive testing, the ORR to tarlatamab was 66.7% with a median of 70% of cells positive. Conclusions: This retrospective analysis supports the use of durvalumab, atezolizumab, lurbinectedin, and tarlatamab regimens in rare NENs other than SCLC. Larger observational trials should identify sequencing data and differences in OS between these regimens and among other commonly used treatments. Endpoint Total Number of Patients Outcome Median OS of platinum + etoposide + PD-L1 inhibitor (atezolizumab and durvalumab) Atezolizumab: 24Durvalumab: 7 Atezolizumab: 13.57 moDurvalumab: 14.29 mo ORR of tarlatamab 25 47.6%,95% CI: 41.7-84.8% ORR of tarlatamab if DLL3+ 15 (median DLL3 expression via IHC of 70%) 66.7%,95% CI: 41.7-84.8% ORR of lurbinectedin 19 52.6%,95% CI: 36-78.4% Median PFS of tarlatamab 25 3.29 mo,95% CI: 1.91-7.69 Median PFS of lurbinectedin 19 3.35 months,95% CI: 2.53-8.44 Median OS from first line systemic therapy of patients who received subsequent line tarlatamab versus any other subsequent line therapy Tarlatamab: n=25 Other therapy: n=29 Taralatamab: 14.88 mo,Other therapy: 12.55 mo,HR=0.79, p=0.42 Median OS from first line therapy of patients who received subsequent line lurbinectedin versus those who received any other subsequent line therapy Lurbinectedin: 19Other therapy: 14 Lurbinectedin: 12.88 mo,Other therapy: 12.87 mo,HR=0.98, p=0.97