Department of Medical Oncology, Hospital Universitario 12 de Octubre, Lung Cancer Unit CNIO-H120, Complutense University and Ciberonc, Madrid, Spain.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clin Cancer Res. 2024 Feb 16;30(4):824-835. doi: 10.1158/1078-0432.CCR-23-1689.
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.
在 CASPIAN 试验中，与 EP 单药治疗相比，一线 durvalumab 联合铂类依托泊苷（EP）显著改善了广泛期小细胞肺癌（ES-SCLC）患者的总生存期（OS）。我们报告了根据程序性死亡配体-1（PD-L1）表达和组织肿瘤突变负担（tTMB）对 CASPIAN 结果的探索性分析。
患者按 1:1:1 的比例随机分配至 durvalumab（1500mg）联合 EP、durvalumab 联合 tremelimumab（75mg）联合 EP 或 EP 单药治疗。使用非分层 Cox 比例风险模型估计 PD-L1 和 tTMB 亚组的治疗效果。
PD-L1 和 tTMB 生物标志物可评估人群（BEP）分别占意向治疗人群的 54.4%（438/805）和 35.2%（283/805）。PD-L1 阳性率较低：分别有 5.7%、25.8%和 28.3%的患者肿瘤细胞（TC）上的 PD-L1 表达≥1%、免疫细胞（IC）上的 PD-L1 表达≥1%以及 TC 或 IC 上的 PD-L1 表达≥1%。与 EP 单药治疗相比，durvalumab 联合 EP 治疗在 PD-L1 亚组中的 OS 获益相似，风险比均在 PD-L1 BEP 的 95%置信区间（0.47-0.79）内。与 EP 单药治疗相比，durvalumab 联合 tremelimumab 联合 EP 治疗在 PD-L1≥1%与<1%亚组中的 OS 获益更大，尽管 CI 有重叠。在 OS 方面，tTMB 与治疗效果之间没有证据表明存在交互作用（durvalumab 联合 EP 对比 EP，P=0.916；durvalumab 联合 tremelimumab 联合 EP 对比 EP，P=0.672）。
在 ES-SCLC 患者中，一线 durvalumab 联合 EP 治疗可观察到 OS 获益，无论 PD-L1 或 tTMB 状态如何。PD-L1 表达可能被证明是 PD-（L）1 和 CTLA-4 抑制联合治疗的有用生物标志物，尽管这需要通过独立数据集进行确认。见 Rolfo 和 Russo 的相关评论，第 652 页。
