Liquid Biopsy Testing Can Improve Selection of Advanced Non-Small-Cell Lung Cancer Patients to Rechallenge with Gefitinib

Riziero Esposito Abate, Raffaella Pasquale, Alessandra Sacco, Maria Carmela Piccirillo, Alessandro Morabito, Paolo Bidoli, Giovanna Finocchiaro, Rita Chiari, Luisa Foltran, Roberta Buosi, Marcello Tiseo, Laura Giannetta, Ciro Battiloro, Gianpiero Fasola, Gianpiero Romano, Libero Ciuffreda, Antonio Frassoldati, Filippo de Marinis, Federico Cappuzzo, Nicola Normanno

Research output: Contribution to journalArticlepeer-review


The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (EGFR). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the EGFR exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same EGFR activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4-3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6-5.3 months), resulting in a statistically significant difference (Long rank test p = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing.
Original languageEnglish
Article number1431
Number of pages10
Issue number10
Publication statusPublished - Sep 25 2019


  • liquid biopsy
  • non-small-cell lung cancer
  • p.T790M
  • rechallenge
  • resistance


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