PMID- 35838839 OWN - NLM STAT- MEDLINE DCOM- 20230705 LR - 20230705 IS - 1432-1335 (Electronic) IS - 0171-5216 (Print) IS - 0171-5216 (Linking) VI - 149 IP - 7 DP - 2023 Jul TI - Selective RET inhibitors shift the treatment pattern of RET fusion-positive NSCLC and improve survival outcomes. PG - 2987-2995 LID - 10.1007/s00432-022-04188-7 [doi] AB - 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. CI - (c) 2022. The Author(s). FAU - Lu, Chang AU - Lu C AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Wei, Xue-Wu AU - Wei XW AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Zhang, Yi-Chen AU - Zhang YC AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Chen, Zhi-Hong AU - Chen ZH AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Xu, Chong-Rui AU - Xu CR AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Zheng, Ming-Ying AU - Zheng MY AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Yang, Jin-Ji AU - Yang JJ AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Zhang, Xu-Chao AU - Zhang XC AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. FAU - Zhou, Qing AU - Zhou Q AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. gzzhouqing@126.com. AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. gzzhouqing@126.com. LA - eng GR - Grant No. 81871891 to QZ/National Natural Science Foundation of China/ GR - Grant No. DFJH201810 to QZ/High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ GR - Grant No. KJ012019428 to QZ/GDPH Scientific Research Funds for Leading Medical Talents in Guangdong Province/ PT - Journal Article DEP - 20220715 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (RET protein, human) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics MH - *Lung Neoplasms/drug therapy/genetics/chemically induced MH - Retrospective Studies MH - Proto-Oncogene Proteins c-ret/genetics MH - Protein Kinase Inhibitors/therapeutic use PMC - PMC10314840 OTO - NOTNLM OT - Adverse event OT - Non-small cell lung cancer OT - RET fusion OT - Real-world data OT - Tyrosine kinase inhibitor COIS- The authors declare no competing interests. Qing Zhou reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi, outside the submitted work. Other authors declare no competing interests that could have appeared to influence the work reported in this paper. EDAT- 2022/07/16 06:00 MHDA- 2023/07/05 06:42 PMCR- 2022/07/15 CRDT- 2022/07/15 11:58 PHST- 2022/05/30 00:00 [received] PHST- 2022/07/04 00:00 [accepted] PHST- 2023/07/05 06:42 [medline] PHST- 2022/07/16 06:00 [pubmed] PHST- 2022/07/15 11:58 [entrez] PHST- 2022/07/15 00:00 [pmc-release] AID - 10.1007/s00432-022-04188-7 [pii] AID - 4188 [pii] AID - 10.1007/s00432-022-04188-7 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2023 Jul;149(7):2987-2995. doi: 10.1007/s00432-022-04188-7. Epub 2022 Jul 15.