PMID- 34268392 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220424 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 9 DP - 2021 May TI - The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. PG - 779 LID - 10.21037/atm-20-6910 [doi] LID - 779 AB - BACKGROUND: Fast progression (FP), hyperprogressive disease (HPD), and early death (ED) are the newly reported cancer progression patterns in response to immune checkpoint inhibitor (ICI) treatment. This study aimed to investigate the clinical and genomic characteristics of FP, HPD, and ED following the ICI treatment of advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 117 patients with advanced NSCLC who were treated with ICIs from March 2017 to October 2019. FP was defined as (I) time to treatment failure (TTF) <1.5 months; and (II) >/=50% increase in the sum of the longest diameter (SLD) of target lesions. HPD was defined as (I) TTF <2 months; and (II) >/=50% change in tumor growth rate compared with before ICI initiation. ED was defined as overall survival (OS) <3 months. Tissue samples from 18 FP/HPD/ED patients and 5 partial response (PR) patients were subjected to genomic profiling. Genomic data from 693 tumor mutational burden- and histology-matched lung cancer samples were retrieved from an internal database as a control. RESULTS: FP, HPD, and ED occurred in 7.21%, 9.38%, and 11.97% patients, respectively. The progression-free survival was comparable among the 3 groups. The median overall survival for FP, HPD, and ED were 3.19, 11.2, and 1.84 months, respectively. The genomic landscape revealed 1 EGFR amplification, 1 ALK fusion, 6 KRAS mutations, 1 ERBB2 amplification, 1 MET amplification, and 1 RET fusion among the 18 patients with FP/HPD/ED. Compared with the Control group, ED patients showed higher mutation frequencies for KRAS (P<0.01), CDKN1B (P<0.01), and NTRK1 (P=0.04). Mutations in RAD54L (P=0.018) and MYC (P=0.04) were more common in FP patients; HPD patients showed more frequent RAD54L mutations (P<0.001). CONCLUSIONS: We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Li, Jingwen AU - Li J AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Xiang, Chan AU - Xiang C AD - Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Wang, Yue AU - Wang Y AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhou, Yan AU - Zhou Y AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Cao, Shuhui AU - Cao S AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Ling, Xuxinyi AU - Ling X AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Ye, Junyi AU - Ye J AD - Department of Medicine and Clinical Research, Burning Rock Biotech, Guangzhou, China. FAU - Zheng, Jingjing AU - Zheng J AD - Department of Medicine and Clinical Research, Burning Rock Biotech, Guangzhou, China. FAU - Shao, Lin AU - Shao L AD - Department of Medicine and Clinical Research, Burning Rock Biotech, Guangzhou, China. FAU - Zhong, Hua AU - Zhong H AD - Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Han, Yuchen AU - Han Y AD - Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8246171 OTO - NOTNLM OT - Hyperprogressive disease (HPD) OT - early death (ED) OT - fast progression (FP) OT - immune checkpoint inhibitor (ICI) OT - non-small cell lung cancer (NSCLC) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6910). The authors have no conflicts of interest to declare. EDAT- 2021/07/17 06:00 MHDA- 2021/07/17 06:01 PMCR- 2021/05/01 CRDT- 2021/07/16 06:42 PHST- 2020/10/14 00:00 [received] PHST- 2021/02/04 00:00 [accepted] PHST- 2021/07/16 06:42 [entrez] PHST- 2021/07/17 06:00 [pubmed] PHST- 2021/07/17 06:01 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - atm-09-09-779 [pii] AID - 10.21037/atm-20-6910 [doi] PST - ppublish SO - Ann Transl Med. 2021 May;9(9):779. doi: 10.21037/atm-20-6910.