Dataset Information

Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

ABSTRACT: Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with EGFR-mutated NSCLC treated with EGFR-TKIs were available. Next generation sequencing (NGS) on cfDNA was performed, and plasma TKI concentrations were measured. Patients without complete plasma conversion of EGFR mutation at week 6 had a significantly shorter PFS (5.5 vs. 17.0 months, p = 0.002) and OS (14.0 vs. 25.5 months, p = 0.003) compared to patients with plasma conversion. In thirteen (second line) osimertinib-treated patients with a (plasma or tissue) concomitant TP53 mutation at baseline, PFS was significantly shorter compared to six wild-type cases; 8.8 vs. 18.8 months, p = 0.017. Erlotinib Cmean decrease of ?10% in the second tertile of treatment was also associated with a significantly shorter PFS; 8.9 vs. 23.6 months, p = 0.037. We obtained evidence that absence of plasma loss of the primary EGFR mutation, isolated plasma p.T790M loss after six weeks, baseline concomitant TP53 mutations, and erlotinib Cmean decrease during treatment are probably related to worse outcome.

SUBMITTER: Steendam CMJ

PROVIDER: S-EPMC7692448 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

Steendam Christi M J CMJ Veerman G D Marijn GDM Pruis Melinda A MA Atmodimedjo Peggy P Paats Marthe S MS van der Leest Cor C von der Thüsen Jan H JH Yick David C Y DCY Oomen-de Hoop Esther E Koolen Stijn L W SLW Dinjens Winand N M WNM van Schaik Ron H N RHN Mathijssen Ron H J RHJ Aerts Joachim G J V JGJV Dubbink Hendrikus Jan HJ Dingemans Anne-Marie C AC

Cancers 20201029 11

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with <i>EGFR</i>-mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with <i>EGFR</i>-mutated NSCLC treated with EGF ...[more]

PMID: 33138052

Similar Datasets

Project description:BackgroundAlthough immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.MethodsThe profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.ResultsPatients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (<1%) PD-L1 expression than with positive (≥1%) PD-L1 expression (15.61 vs. 7.40 months, p = 0.138). Median PFS and OS were significantly shorter in heavily treated patients (prior lines of therapy ≥3 lines vs. <3 lines: mPFS, 1.80 vs. 2.50 months, p = 0.003; mOS, 6.70 vs. 14.00 months, p = 0.031). ORR was also lower in patients who had received ≥3 prior lines of therapy compared to in those <3 prior lines of therapy (0.00% vs. 21.67%, p = 0.002).ConclusionPatients with major EGFR mutations showed poorer responses to ICIs than those with rare EGFR mutations. EGFR-mutated patients with lower PD-L1 expression showed a trend towards a longer OS after receiving ICIs. ICIs should be administered as early as possible to previously treated EGFR-mutated NSCLC patients. ICI-based combined therapies may be a direction for treatment of these patient subtypes in the future.

Dataset Information

Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

Publications

Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets