Dataset Information

High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.

ABSTRACT: Purpose:Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). Methods:We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group. Results:Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ? 50%, 1-49%, and <1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ? 50% than in the other groups (43.5% vs 72.1% vs 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ? 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004) and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ? 50% than in the other groups (13.3% vs 40.0% vs 53.3%, all p = 0.001). PD-L1 TPS ? 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043). Conclusion:High PD-L1 expression was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.

SUBMITTER: Yoon BW

PROVIDER: S-EPMC7445533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in <i>EGFR</i>-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.

Yoon Byung Woo BW Chang Boksoon B Lee Seung Hyeun SH

OncoTargets and therapy 20200820

<h4>Purpose</h4>Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (<i>EGFR</i>)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs).<h4>Methods</h4>We retrospectively enrolled < ...[more]

PMID: 32903896

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Project description:PurposeReactive oxygen species modulator 1 (Romo1) is a novel protein that regulates the production of intracellular reactive oxygen species. Romo1 has been shown to be associated with poor survival in various clinical settings for the treatment of lung cancer. In this study, we evaluated whether tissue Romo1 expression was associated with clinical outcomes in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).MethodRomo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by histologic score. Univariate and multivariate analyses were performed to identify the clinicopathologic parameters, including Romo1 expression, which may be associated with progression-free survival (PFS), overall survival (OS), and incidence of secondary T790M mutation.ResultsA total of 96 tumor specimens were analyzed. With the cut-off value of 200, 71 (74.0%) and 25 (26.0%) patients were classified into low and high Romo1 groups, respectively. The median PFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (13.1 vs 19.9 months, p = 0.0165). The median OS of the high Romo1 group was also significantly shorter than that of the low Romo1 group (19.8 vs 37.0 months, p = 0.0006). Multivariate analyses showed that high Romo1 expression was independently associated with both poor PFS (hazard ratio [HR] = 2.48, 95% confidence interval [CI]: 1.35-4.56, p = 0.0034) and poor OS (HR = 3.17, 95% CI: 1.57-6.41, p = 0.0013). In addition, the rate of secondary T790M mutation after TKI failure was significantly lower in the high Romo1 group than the low Romo1 group (16.7% vs. 38.3%, p = 0.0369).ConclusionsRomo1 overexpression was associated with poor response to treatment and short survival in patients treated with EGFR-TKIs, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach. In addition, our data highlight that Romo1 could be a potential predictive and prognostic biomarker for this patient population.

Dataset Information

High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.

Publications

High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in <i>EGFR</i>-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.

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