PRECISIONheor, New York, NY.
Center for Observational and Real-World Evidence, Merck & Co., Inc., Rahway, NJ.
J Immunother. 2024 May 1;47(4):128-138. doi: 10.1097/CJI.0000000000000500. Epub 2023 Dec 19.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
由于分子检测技术的进步以及新的靶向治疗和免疫疗法的发展，晚期或转移性非小细胞肺癌（NSCLC）患者的治疗选择正在迅速发展。然而，对于携带 BRAF V600E 突变、HER2/ERBB2 改变、MET 外显子 14 跳跃突变或 RET 重排的晚期或转移性 NSCLC 患者，PD-1/PD-L1 抑制剂的疗效尚不完全清楚。系统文献回顾旨在总结临床试验和观察性研究中关于肿瘤表达这些生物标志物且接受 PD-1/PD-L1 抑制剂治疗的患者的客观缓解率、无进展生存期和总生存期的证据。对 Embase、MEDLINE、会议摘要和临床试验登记处进行了检索，共确定了 12 项独特的研究：4 项研究纳入了携带 BRAF V600E 突变的患者，6 项研究纳入了携带 HER2/ERBB2 改变的患者，7 项研究纳入了携带 MET 外显子 14 跳跃突变的患者，5 项研究纳入了携带 RET 重排的患者。在各项研究中，治疗和患者特征存在异质性，并且许多重要的预测和预后因素的报告不足，包括治疗方案、患者的治疗线数和肿瘤 PD-L1 表达，这可能解释了研究之间客观缓解率、无进展生存期和总生存期的广泛差异。因此，需要前瞻性评估 PD-1/PD-L1 抑制剂在晚期或转移性 NSCLC 患者中的临床疗效，这些患者的肿瘤携带新兴的预测或预后生物标志物，以确定这类免疫疗法是否能为这些患者提供额外的生存获益。
