Abstract
e21653 Background: Hyperprogressive disease (HPD), characterized by a rapid increase in tumor growth rate (TGR), has been reported in 13.8% NSCLC patients (pts) treated with ICI. Besides, 10.4% of NSCLC pts experience FP (fast progression) and/or early dearth (ED) upon atezolizumab. Although defined differentially, it has been shown that these progression patterns have overlapped portions. The molecular characteristics in different progression patterns have not been well elucidated and compared. Methods: 117 advanced LC pts treated with ICI were recruited, whose progression pattern was assessed according to the following criteria: FP was defined as ≥ 50% increase in the sum of long diameters within 6 weeks (wks) of ICI start; ED was defined as deaths within 12 wks. HPD was defined as the change in TGR greater than 50% compared with that prior to the initiation of ICI (TGR2/TGR1 > 1.5). There were 14, 8 and 9 ED, FP and HPD patients respectively. 5 patients were qualified for than one definition and 1 patient qualified for all 3 definitions. Tissue samples from 36 pts (18 FP/ED/HPD patients) were subjected to genomic profiling using a panel of 520 cancer-related genes. For genomic comparison, additional 693 non-HPD, non-ED and non-FP LC samples with matched TMB and histology were retrieved from our internal database. Results: The FP, HPD and ED occurred in 7.21%, 9.38% and 11.97% pts, respectively. The PFS was comparable among the 3 groups (P = 0.541). The median OS for FP, HPD and ED was 3.19, 11.2 and 1.84 months, respectively (P < 0.001). The genomic landscape of 18 FP/ED/HPD pts revealed 1 EGFR amp, 1 ALK fusion, 6 KRAS mutations, 1 ERBB2 amp, 1 MET amp and 1 RET fusion. Two ED pts harbored concomitant STK11 and KRAS mutations. MDM2 and MDM4 mutations co-occurred in 1 ED patient. 1 patient with ED and HPD had MDM4 mutation. Genomic comparison analysis revealed that ED pts had higher mutation frequency in KRAS (P < 0.01) and CDKN1B (P < 0.01) comparing with the 693 controls. Furthermore, FP pts were more likely to have RAD54L (p = 0.018) an MYC (p = 0.04) mutations. HPD pts showed higher rate of RAD54L (P < 0.001) and ARID1A (p = 0.04) than controls. Conclusions: We revealed FP, HPD and ED have comparable PFS but significant difference is OS. We also demonstrated different genomic characteristics associated with different progression patterns upon ICI treatment, which might further facilitate clinicians to stratify pts for ICI therapy.
Published Version
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