Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.
BMC Cancer. 2024 Nov 19;24(1):1427. doi: 10.1186/s12885-024-13155-z.
Selective RET inhibitors have been approved by the Chinese government for the treatment of RET-rearranged non-small cell lung cancer. This study aimed to illustrate the efficacy and safety of selective RET inhibitors in a real-world clinical context in China.
Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring RET rearrangement and receiving RET tyrosine kinase inhibitors (RET-TKI) in the real world were enrolled in this retrospective study. Clinical data, including baseline clinicopathological information, efficacy parameters such as objective response rate (ORR) and progression-free survival (PFS), and adverse events (AEs), were collected from the electronic medical record system. The pattern of treatment failure of first-line RET-TKI was also described.
Fifty-one patients were enrolled in this study. RET-TKI induced an ORR of 73.1% and a median PFS (mPFS) of 22.7 months (95%CI, 11.7-33.7) in the first-line setting. The ORR and mPFS were 58.3% and 17.7 months (95%CI, 9.1-26.2), 55.6% and 14.7 months (95%CI, 12.6-16.8) in the second-line and later-line settings, respectively. No significant difference was observed among different application lines with respect to the ORR (P = 0.534) or PFS (P = 0.795). In the first-line setting, RET-TKI significantly prolonged PFS compared to other regimens including chemotherapy-based regimens, multikinase inhibitors and other systemic regimens without chemotherapy (P < 0.05). Poor ECOG performance status was related to shorter PFS (P = 0.018). The most common AEs of grade 3 or worse were a decreased neutrophil count (11.4%) and anemia (11.4%). No new AEs or grade 5 AEs were observed. Brain metastasis was one of the most common patterns of treatment failure. In patients with baseline brain metastasis, the intracranial ORR was 50%, and the DCR was 100%.
RET-TKI had favorable efficacy and safety in real-world contexts in China and should be considered the preferred choice for first-line treatment in RET-rearranged NSCLC patients.
中国政府已批准选择性 RET 抑制剂用于治疗 RET 重排的非小细胞肺癌。本研究旨在阐明选择性 RET 抑制剂在真实世界临床环境中的疗效和安全性。
本回顾性研究纳入了接受 RET 酪氨酸激酶抑制剂（RET-TKI）治疗的局部晚期或转移性非小细胞肺癌（NSCLC）患者，这些患者存在 RET 重排。从电子病历系统中收集了包括基线临床病理信息、疗效参数（客观缓解率[ORR]和无进展生存期[PFS]）和不良事件（AE）在内的临床数据。还描述了一线 RET-TKI 治疗失败的模式。
本研究共纳入 51 例患者。一线治疗中，RET-TKI 诱导的 ORR 为 73.1%，中位 PFS（mPFS）为 22.7 个月（95%CI，11.7-33.7）。二线及以后线治疗的 ORR 和 mPFS 分别为 58.3%和 17.7 个月（95%CI，9.1-26.2）、55.6%和 14.7 个月（95%CI，12.6-16.8）。不同应用线之间的 ORR（P=0.534）或 PFS（P=0.795）无显著差异。在一线治疗中，与包括基于化疗的方案、多激酶抑制剂和无化疗的其他全身方案相比，RET-TKI 显著延长了 PFS（P<0.05）。ECOG 表现状态较差与较短的 PFS 相关（P=0.018）。最常见的 3 级或更高级别的不良事件为中性粒细胞计数降低（11.4%）和贫血（11.4%）。未观察到新的不良事件或 5 级不良事件。脑转移是治疗失败的最常见模式之一。基线时有脑转移的患者颅内 ORR 为 50%，DCR 为 100%。
RET-TKI 在真实世界环境中的疗效和安全性良好，应作为 RET 重排 NSCLC 患者一线治疗的首选。
