Department of Oncology, the First Medical Center of PLA General Hospital, (Chinese PLA Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs (Ministry of Education, China)), Beijing, 100853, China.
Graduate School, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, 100853, China.
BMC Pulm Med. 2024 Nov 4;24(1):552. doi: 10.1186/s12890-024-03371-5.
The present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population.
The study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE).
A retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3-4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population.
This study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.
本研究旨在全面综述中国 RET 重排实体瘤领域的研究进展，重点关注晚期非小细胞肺癌（NSCLC）患者的真实世界治疗策略和临床结局。本研究深入评估了靶向 RET 抑制剂的治疗效果，并仔细研究了中国患者群体中使用的各种治疗方法。
本研究对中国学者在 RET 驱动基因领域的进展进行了全面综述。分析了实体瘤中 RET 重排的发生率，以及不同治疗模式及其在中国的现状。采用 RECIST 1.1 标准，评估了接受不同治疗方法的 RET 阳性 NSCLC 患者的治疗效果。此外，根据常见不良事件术语标准（CTCAE）对治疗相关不良事件（TRAEs）进行了细致分级。
本研究进行了一项回顾性、多中心的真实世界分析，共纳入 64 例 2015 年 12 月至 2023 年 11 月间经病理证实的 RET 重排晚期 NSCLC 患者。值得注意的是，KIF5B-RET 是最常见的 RET 融合伙伴，占 59.4%。这些患者的治疗干预包括特定的靶向抑制剂，如普拉替尼（48.4%）、化疗（34.3%）、多靶点抑制剂（15.6%）和 1 例（1.6%）免疫治疗联合抗血管生成治疗。在无进展生存期（PFS）方面，普拉替尼单药治疗的中位 PFS 为 16.03 个月，优于化疗（2.87 个月；p<0.0001）、化疗联合抗血管生成治疗（6.90 个月；p=0.048）和多靶点抑制剂（2.50 个月；p<0.0001）。此外，普拉替尼单药治疗的 1 年和 2 年总生存率（OS）分别为 64.3%和 46.4%。关于安全性，71.0%接受普拉替尼治疗的患者出现至少 1 次不良事件，其中 45.2%的不良事件严重程度为 3-4 级。值得注意的是，没有死亡与不良事件相关。常见的不良事件包括血红蛋白减少（35.5%）和中性粒细胞减少（32.3%），表明普拉替尼在该患者人群中总体安全性良好。
本研究总结了中国医疗保健领域中 RET 重排实体瘤的研究进展和治疗方法，特别强调了真实世界中多样化的治疗方法及其在中国晚期 RET 重排 NSCLC 患者中的疗效。值得注意的是，普拉替尼等靶向 RET 抑制剂已成为有效的治疗药物，在该患者群体中显示出显著的疗效和良好的安全性。这些发现突显了普拉替尼和类似的靶向治疗作为 RET 融合阳性 NSCLC 患者新型治疗选择的潜力。
