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

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

doi:10.1158/1078-0432.c.7077758

Abstract

<div>AbstractPurpose: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).Experimental Design: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.Results: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).Conclusions: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.<a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-3087" target="_blank">See related commentary by Rolfo and Russo, p. 652</a></div>

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