Selective RET inhibitors shift the treatment pattern of RET fusion-positive NSCLC and improve survival outcomes

Authors：Lu, Chang; Wei, Xue-Wu; Zhang, Yi-Chen; Chen, Zhi-Hong; Xu, Chong-Rui; Zheng, Ming-Ying; Yang, Jin-Ji; Zhang, Xu-Chao; Zhou, Qing^*

Source：Journal of Cancer Research and Clinical Oncology, 2023, 149(7): 2987-2995.

DOI：10.1007/s00432-022-04188-7

• Non-small cell lung cancer
• RET fusion
• Real-world data
• Tyrosine kinase inhibitor
• Adverse event

Purpose Rearranged during transfection (RET) fusions are important genetic drivers in non-small cell lung cancer (NSCLC). Selective RET inhibitors are setting a new paradigm in RET-driven NSCLC. However, the real-world treatment patterns, outcomes and toxicity remain largely unknown. Methods Data from RET fusion-positive NSCLC patients treated in our centre were retrospectively analysed. Of them, patients diagnosed before and after August 2018 were included in analysis of treatment patterns; and patients received selective RET inhibitors were eligible for analysis of adverse events (AEs). Results Patients diagnosed before August 2018 (n = 30) predominantly received chemotherapy and immunotherapy (83%) as initial therapy, while patients diagnosed after August 2018 (n = 39) mainly received selective RET inhibitors (38.5% at first-line; 50.0% at second-line). In the total 69 patients, overall survival (OS) was prolonged in patients treated with selective RET inhibitors versus untreated patients (median 34.3 versus 17.5 months; p = 0.002) during a median follow-up of 28.7 months. But there was no difference between patients treated with immunotherapy versus untreated patients. In the 38 patients received selective RET inhibition, median progression-free survival (PFS) was 11.9 months. AEs >= grade 3 occurred in 42.1% patients and were not associated with PFS (p = 0.63) or OS (p = 0.60). Haematological toxicity >= grade 3 occurred in 31.6% patients and was the leading cause of drug discontinuation. Conclusion Selective RET inhibitors are increasingly being adopted into clinical practice and are associated with improved OS. However, treatment-related >= grade 3 AEs, especially haematologic AEs, occur frequently in real-world setting.

• Institution
  广东省人民医院; 南方医科大学