In:
Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-07-11)
Abstract:
Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICIs), and how these might differ from features predictive of short-term response (STR). Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs over ten years. LTR and STR were defined as response ≥ 24 months and response & lt; 12 months, respectively. Tumor PD-L1 expression, mutational burden (TMB), next-generation sequencing, and whole exome sequencing data were analyzed to identify characteristics enriched in patients achieving LTR compared to STR and non-LTR. Results: Among 3118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival of 81% and 18% among LTR and STR patients respectively. High TMB (≥ 50th percentile) enriched for LTR compared to STR (P = 0.001) and non-LTR (P & lt; 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared to non-LTR (P & lt; 0.001); PD-L1 ≥ 50% did not enrich for LTR compared to STR (P = 0.181). Non-squamous histology (P = 0.040) and increasing depth of response (median best overall response [BOR] -65% vs -46%, P & lt; 0.001) also associated with LTR compared to STR; no individual genomic alterations were uniquely enriched among LTR patients. Conclusions: Among advanced NSCLC patients treated with ICIs, distinct features including high TMB, non-squamous histology, and depth of radiographic improvement distinguish patients poised to achieve long-term response compared to initial response followed by progression, whereas high PD-L1 does not.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-23-1207
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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