School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, NY, USA.
Curr Med Res Opin. 2022 Aug;38(8):1361-1368. doi: 10.1080/03007995.2022.2078101. Epub 2022 May 31.
This systematic literature review examines the current immune checkpoint inhibitors treatment paradigms, treatment gaps and unmet needs for treating SCLC with respect to efficacy, safety, health related quality of life (HRQoL) and cost-effectiveness.
A search strategy was developed and executed using the National Library of Medicine bibliographic database (PubMed), Cochrane Library, Embase and Google Scholar. Data regarding efficacy, safety, cost-effectiveness and HRQoL were extracted and entered in a data extraction sheet created a priori.
A total of 4961 patients were comprised in all the 12 studies combined. All the studies focus on extensive stage SCLC (ES-SCLC) and not limited stage SCLC (LS-SCLC). All studies used an ICI as the intervention arm and chemotherapy as the control arm. A statistically significant increase in overall survival (OS) and progression free survival (PFS) was observed when ICIs were added to chemotherapy, especially atezolizumab and durvalumab. ICIs in SCLC resulted in immune-related toxicities that have been well-documented in prior immunotherapy trials; their addition to cytotoxic chemotherapy did not worsen chemotherapy-related toxicities. Out of 12 studies, only 3 (25%) included measures to assess the impact of immunotherapy on SCLC patients' HRQoL. Although domain level scores were limited, the addition of ICIs did not seem to worsen symptoms. Two studies conducted a cost-effectiveness analysis of the combination of atezolizumab plus chemotherapy vs. chemotherapy. The addition of atezolizumab to chemotherapy was not found to be cost-effective in either study.
Combining ICIs with chemotherapy enhanced OS and PFS as well as not worsening HRQoL. Among all ICIs, PD-L1 inhibitors showed better effectiveness. Future studies should focus on real-world settings and more clinical trials using ICIs for not only ES-SCLC but also LS-SCLC.
本系统文献综述考察了目前免疫检查点抑制剂治疗小细胞肺癌的治疗模式、治疗差距和未满足的需求,涉及疗效、安全性、健康相关生活质量(HRQoL)和成本效益。
制定了检索策略,并使用美国国立医学图书馆书目数据库(PubMed)、考科兰图书馆、Embase 和 Google Scholar 进行了检索。提取了关于疗效、安全性、成本效益和 HRQoL 的数据,并在预先创建的数据提取表中输入。
共有 4961 名患者纳入了 12 项研究。所有研究均聚焦于广泛期小细胞肺癌(ES-SCLC),而非局限期小细胞肺癌(LS-SCLC)。所有研究均采用免疫检查点抑制剂(ICI)作为干预组,化疗作为对照组。当 ICI 联合化疗时,观察到总生存期(OS)和无进展生存期(PFS)有显著增加,尤其是阿替利珠单抗和度伐利尤单抗。在小细胞肺癌中,ICI 导致免疫相关毒性,在之前的免疫治疗试验中已有详细记录;其与细胞毒性化疗联合使用并未加重化疗相关毒性。在 12 项研究中,仅有 3 项(25%)包括评估免疫疗法对小细胞肺癌患者 HRQoL 影响的措施。尽管域级评分有限,但添加 ICI 似乎并未加重症状。有两项研究对阿替利珠单抗联合化疗与化疗进行了成本效益分析。在这两项研究中,阿替利珠单抗联合化疗均未显示出成本效益。
ICI 联合化疗可提高 OS 和 PFS,且不会降低 HRQoL。在所有 ICI 中,PD-L1 抑制剂显示出更好的疗效。未来的研究应侧重于真实世界的情况,并开展更多临床试验,不仅针对 ES-SCLC,还针对 LS-SCLC 使用 ICI。