TY - JOUR
T1 - Liquid biopsy testing can improve selection of advanced non-small-cell lung cancer patients to rechallenge with gefitinib
AU - Abate, Riziero Esposito
AU - Pasquale, Raffaella
AU - Sacco, Alessandra
AU - Piccirillo, Maria Carmela
AU - Morabito, Alessandro
AU - Bidoli, Paolo
AU - Finocchiaro, Giovanna
AU - Chiari, Rita
AU - Foltran, Luisa
AU - Buosi, Roberta
AU - Tiseo, Marcello
AU - Giannetta, Laura
AU - Battiloro, Ciro
AU - Fasola, Gianpiero
AU - Romano, Gianpiero
AU - Ciuffreda, Libero
AU - Frassoldati, Antonio
AU - Marinis, Filippo De
AU - Cappuzzo, Federico
AU - Normanno, Nicola
PY - 2019/10
Y1 - 2019/10
N2 - The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the effcacy, 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 rechallengefrom 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.
AB - The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the effcacy, 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 rechallengefrom 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.
KW - Liquid biopsy
KW - Non-small-cell lung cancer
KW - P.T790M
KW - Rechallenge
KW - Resistance
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U2 - 10.3390/cancers11101431
DO - 10.3390/cancers11101431
M3 - Article
AN - SCOPUS:85073470745
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 1431
ER -