Vince Megan, Naqvi Syeda Mahrukh Hussnain, Pellini Bruna, Verbosky Michael, Melzer Dan
Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.
Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Lung Cancer. 2024 Dec;198:107999. doi: 10.1016/j.lungcan.2024.107999. Epub 2024 Oct 28.
Small cell lung cancer (SCLC) is an aggressive disease associated with high relapse rates and limited treatment options. Current standard of care treatment for extensive-stage disease includes combination chemotherapy plus immunotherapy. Programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are preferred first-line treatments in combination with chemotherapy with both atezolizumab and durvalumab being equivalent options. Although both ICIs are listed as front-line options in clinical guidelines, there have been no head-to-head trials comparing durvalumab to atezolizumab. Therefore, it is unknown if either agent is superior with regards to efficacy or safety.
This retrospective, single-institution study examined patients with extensive-stage small cell lung cancer presenting to Moffitt Cancer Center between October 1st, 2018 to May 31st, 2023 who received either atezolizumab or durvalumab in combination with a platinum-doublet in the first-line setting. To be included in this analysis patients must have received at least two cycles of induction chemotherapy and ICI and one cycle of maintenance ICI. The primary outcome of this study was overall survival. The secondary outcomes include progression-free survival, immune-related adverse events, hospitalizations due to ICIs, and progression-free survival on second-line therapy (PFS2).
Of the 101 patients included, 55 received durvalumab (54.5 %) and 46 received atezolizumab (45.5 %). The median overall survival in the durvalumab and atezolizumab arms were 14.7 versus 11.6 months, respectively (HR 0.59; 95 % CI, 0.38-0.92; P = 0.020). There was not a statistically significant difference in median progression-free survival between the two arms (6.3 versus 5.9 months, P = 0.344). Atezolizumab was associated with a numerically higher incidence of immune-related adverse events (47.8 % versus 32.7 %, P = 0.157) and hospitalization rates for those with an immune-related adverse event (36.4 % versus 16.7 %, P = 0.204). PFS2 was 2.3 months in the atezolizumab arm and 3.4 months in the durvalumab arm (HR 1.24; 95 % CI, 0.69-2.23; P = 0.466).
In this real-world retrospective study, durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer consistent with previous findings from a similar study in a Chinese patient population. Although not statistically significant, there was a lower incidence of immune-related adverse events in the durvalumab arm as well as ICI-related hospitalizations. PFS2 was not statistically significant different between arms.
小细胞肺癌（SCLC）是一种侵袭性疾病，复发率高且治疗选择有限。广泛期疾病的当前标准治疗方案包括联合化疗加免疫疗法。程序性死亡配体-1（PD-L1）免疫检查点抑制剂（ICI）是与化疗联合使用的首选一线治疗方法，阿替利珠单抗和度伐利尤单抗都是等效选择。尽管两种ICI在临床指南中均被列为一线选择，但尚未有将度伐利尤单抗与阿替利珠单抗进行头对头比较的试验。因此，尚不清楚这两种药物在疗效或安全性方面是否有优劣之分。
这项回顾性单机构研究检查了2018年10月1日至2023年5月31日期间就诊于莫菲特癌症中心的广泛期小细胞肺癌患者，这些患者在一线治疗中接受了阿替利珠单抗或度伐利尤单抗联合铂类双药化疗。纳入该分析的患者必须接受至少两个周期的诱导化疗和ICI以及一个周期的维持ICI。本研究的主要结局是总生存期。次要结局包括无进展生存期、免疫相关不良事件、因ICI导致的住院以及二线治疗的无进展生存期（PFS2）。
在纳入的101例患者中，55例接受了度伐利尤单抗（54.5%），46例接受了阿替利珠单抗（45.5%）。度伐利尤单抗组和阿替利珠单抗组的中位总生存期分别为14.7个月和11.6个月（HR 0.59；95%CI，0.38 - 0.92；P = 0.020）。两组之间的中位无进展生存期无统计学显著差异（6.3个月对5.9个月，P = 0.344）。阿替利珠单抗与免疫相关不良事件的发生率在数值上较高（47.8%对32.7%，P = 0.157），以及免疫相关不良事件患者的住院率（36.4%对16.7%，P = 0.204）。阿替利珠单抗组的PFS2为2.3个月，度伐利尤单抗组为3.4个月（HR 1.24；95%CI，0.69 - 2.23；P = 0.466）。
在这项真实世界回顾性研究中，度伐利尤单抗与广泛期小细胞肺癌患者的总生存期改善相关，这与之前在中国患者群体中进行的类似研究结果一致。尽管无统计学显著差异，但度伐利尤单抗组免疫相关不良事件以及ICI相关住院的发生率较低。两组之间的PFS2无统计学显著差异。
