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

• Published in: Cancers Vol. 12; no. 11; p. 3179
• Main Authors: Steendam, Christi M J, Veerman, G D Marijn, Pruis, Melinda A, Atmodimedjo, Peggy, Paats, Marthe S, van der Leest, Cor, von der Thüsen, Jan H, Yick, David C Y, Oomen-de Hoop, Esther, Koolen, Stijn L W, Dinjens, Winand N M, van Schaik, Ron H N, Mathijssen, Ron H J, Aerts, Joachim G J V, Dubbink, Hendrikus Jan, Dingemans, Anne-Marie C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-10-2020; MDPI
• Subjects: Genetic aspects; Lung cancer, Non-small cell; Netherlands; TKI; NSCLC; cfDNA; pharmacokinetics; plasma conversion; TP53 mutation; EGFR; T790M mutation
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12113179

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with
-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
-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
mutation at week 6 had a significantly shorter PFS (5.5 vs. 17.0 months,
= 0.002) and OS (14.0 vs. 25.5 months,
= 0.003) compared to patients with plasma conversion. In thirteen (second line) osimertinib-treated patients with a (plasma or tissue) concomitant
mutation at baseline, PFS was significantly shorter compared to six wild-type cases; 8.8 vs. 18.8 months,
= 0.017. Erlotinib C
decrease of ≥10% in the second tertile of treatment was also associated with a significantly shorter PFS; 8.9 vs. 23.6 months,
= 0.037. We obtained evidence that absence of plasma loss of the primary
mutation, isolated plasma p.T790M loss after six weeks, baseline concomitant
mutations, and erlotinib C
decrease during treatment are probably related to worse outcome.