American Association for Cancer Research
ccr-23-1689_supplementary_figure_s1_suppfs1.pdf (185.63 kB)

Supplementary Figure S1 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden

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journal contribution
posted on 2024-02-16, 09:00 authored by Luis Paz-Ares, Marina Chiara Garassino, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Artem Poltoratskiy, Dmytro Trukhin, Maximilian J. Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Galina Statsenko, Nikolay Conev, Igor Bondarenko, Libor Havel, György Losonczy, Mingchao Xie, Zhongwu Lai, Nadia Godin-Heymann, Helen Mann, Haiyi Jiang, Yashaswi Shrestha, Jonathan W. Goldman

Sample flow for biomarker analysis.



In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB). Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model. The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672). OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset.See related commentary by Rolfo and Russo, p. 652

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