Platinum-sensitive relapsed SCLC: What is the best option? A meta-analysis.

Abstract

e20155 Background: Small cell lung cancer (SCLC) remains highly aggressive with high relapse rates despite platinum-based chemotherapy. For relapse ≥ 90days after first line therapy (platinum sensitive relapse), current standards include Topotecan, Lurbinectedin, and platinum-rechallenge. Tarlatamab (novel delta-like ligand 3-targeting bispecific antibody) was recently FDA approved for platinum-resistant SCLC. The cost and administration challenges of Tarlatamab remain barriers to its widespread use. It may offer superior efficacy in the platinum-sensitive relapsed population; however, comparative studies to current regimens are lacking. Methods: Systematic review with PubMed and Embase identified studies reporting outcomes of Tarlatamab (n = 6), Topotecan (n = 16), Lurbinectedin (n = 10), and platinum-rechallenge (n = 13) in platinum-sensitive relapsed SCLC. 45 studies met the inclusion criteria. Overall survival (OS) and progression-free survival (PFS) were compared using one-way ANOVA with Tukey post-hoc tests and median survival ratio (MSRs) analysis. Multivariate regression evaluated age, brain/liver metastasis, ECOG functional status, and toxicology profiles as potential effect modifiers. Effect sizes were reported with 95% confidence interval, and p < 0.05 was used for statistical significance. Results: Across 45 studies, mean OS was 11.9 months (Tarlatamab), 11.8 months (platinum rechallenge), 7.8 months (Lurbinectedin), and 7.4 months (Topotecan); mean PFS was 4.0, 5.1, 4.3, and 2.9 months, respectively. There were significant differences between regimens for both OS (F = 6.67, p = 0.001) and PFS (F = 8.31, p < 0.001). Compared with Tarlatamab, platinum-rechallenge had similar OS (p = 0.999); Lurbinectedin had shorter OS (p = 0.07); and Topotecan had significantly shorter OS (p = 0.003). All treatments significantly outperformed Topotecan for PFS (p = 0.028), with platinum-rechallenge achieving the highest PFS. MSR analysis confirmed tarlatamab to be equivalent to platinum-rechallenge, but superior to Topotecan and Lurbinectedin. Conclusions: In platinum-sensitive relapsed SCLC, Tarlatamab is a competitive second-line option, with survival outcomes superior to chemotherapy but no clear superiority over platinum-rechallenge. Treatment selection should be individualized based on patient/tumor factors and clinical context. However, given Tarlatamab's high acquisition cost and specialized administration, prospective randomized trials directly comparing Tarlatamab with platinum rechallenge will be useful for exploring the specific regimen, patient, and tumor characteristics that benefit from Tarlatamab.