Abstract Background PD‐L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non–small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD‐L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD‐L1 in NSCLC cytology specimens is explored. Methods Next‐generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno‐oncology signatures. TMB and PD‐L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations. Results Of the 312 cases evaluated, 192 harbored NSCLC‐specific oncogenic alterations. Relative to EGFR ‐mutated tumors, TMB was significantly higher in KRAS ( p adj = 2.7 × 10 −4 ), ERBB2 ( p adj = .023), and BRAF ( p adj = .023) ‐mutated tumors but lower in ALK ‐rearranged tumors ( p adj = .005). Significantly higher PD‐L1 expression was seen in tumors with KRAS ( p adj = .002) and MET exon 14 ( p adj = 1.06 × 10 −4 ) when compared to EGFR ‐mutated tumors. Strong positive correlations between TMB and PD‐L1 were observed in ERBB2 ‐, KRAS ‐, and BRAF ‐mutated tumors when evaluated as continuous variables. TP53 mutations further enhanced immunogenicity when co‐occurring with KRAS , ERBB2 , or BRAF mutations but this effect was not observed in EGFR ‐mutated tumors. Conclusions These findings demonstrate distinct TMB and PD‐L1 profiles that may identify patients who will benefit from ICI therapy. Cytology specimens provide adequate material for biomarker testing, which underscores their value in guiding immunotherapy decisions.
Dai et al. (Fri,) studied this question.
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