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Open AccessArticle

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

1
Cell Biology and Biotherapy Unit, Istiuto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, 80131 Naples, Italy
2
Clinical Trials Unit, Istituto Nazionale Tumori, IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
3
Medical Oncology, Thoracic Department, Istiuto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, 80131 Napoli, Italy
4
Department of Oncology, Azienda Socio Sanitaria Territoriale (ASST) Monza, Presidio San Gerardo, 20900 Monza, Italy
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Department of Oncology & Hematology, Humanitas Clinical & Research Center, 20089 Rozzano (MI), Italy
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Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, 06129 Perugia, Italy
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Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCSS, 33081 Aviano, Italy
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Department of Medical Oncology, Ospedale Santo Spirito, 15033 Casale Monferrato, Italy
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Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
10
Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy
11
Division of Pulmonary Oncology, Azienda Ospedaliera Dei Colli Monaldi, 80131 Naples, Italy
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Azienda Ospedaliera Universitaria Santa Maria della Misericordia, 33100 Udine, Italy
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Presidio Ospedaliero Vito Fazzi, 73100 Lecce, Italy
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AOU Città della salute e della Scienza di Torino, 10126 Turin, Italy
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Arcispedale S. Anna, Ferrara 44124, Italy
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Division of Thoracic Oncology, European Institute of Oncology, IRCCS, 20122 Milan, Italy
17
Director Oncology and Hematology Department, AUSL Romagna, 48121 Ravenna, Italy
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Cancers 2019, 11(10), 1431; https://doi.org/10.3390/cancers11101431
Received: 7 August 2019 / Revised: 19 September 2019 / Accepted: 20 September 2019 / Published: 25 September 2019
(This article belongs to the Special Issue Epidermal Growth Factor Receptor Signaling in Cancer)
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. View Full-Text
Keywords: non-small-cell lung cancer; rechallenge; resistance; liquid biopsy; p.T790M non-small-cell lung cancer; rechallenge; resistance; liquid biopsy; p.T790M
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Esposito Abate, R.; Pasquale, R.; Sacco, A.; Piccirillo, M.C.; Morabito, A.; Bidoli, P.; Finocchiaro, G.; Chiari, R.; Foltran, L.; Buosi, R.; Tiseo, M.; Giannetta, L.; Battiloro, C.; Fasola, G.; Romano, G.; Ciuffreda, L.; Frassoldati, A.; de Marinis, F.; Cappuzzo, F.; Normanno, N. Liquid Biopsy Testing Can Improve Selection of Advanced Non-Small-Cell Lung Cancer Patients to Rechallenge with Gefitinib. Cancers 2019, 11, 1431.

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