The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report
Marzia Del Re,
Eleonora Rofi,
Carla Cappelli,
Gianfranco Puppo,
Stefania Crucitta,
Simona Valeggi,
Antonio Chella,
Romano Danesi,
Iacopo Petrini
Affiliations
Marzia Del Re
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa
Eleonora Rofi
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa
Carla Cappelli
Unit of Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University Hospital of Pisa
Gianfranco Puppo
Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital of Pisa
Stefania Crucitta
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa
Simona Valeggi
Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital of Pisa
Antonio Chella
Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital of Pisa
Romano Danesi
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa
Iacopo Petrini
Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital of Pisa
Abstract Background Systemic treatment of advanced non-small cell lung cancer (NSCLC) has changed dramatically since the introduction of targeted therapies. The analysis of circulating tumor DNA (ctDNA) is a valuable approach to monitor the clonal evolution of tumors during treatment with EGFR-tyrosine kinase inhibitors (TKIs) and to detect resistance mutations. Case presentation A NSCLC patient with exon 19 deletion (ex19del) of EGFR was treated with osimertinib after multiple lines of treatment and obtained a partial response that lasted over 26 months. Blood was collected at each visit and ctDNA was extracted to monitor ex19del by digital droplet PCR. Within a few weeks from the beginning of osimertinib, ex19del disappeared from plasma but appeared again and steadily increased a few months later anticipating tumor progression. Interestingly, the change in ex19del was much more pronounced than other mutations, since T790M appeared 3 months after the increase of ex19del, and C797S was detectable a few weeks before clinical disease progression. Then the patient received cytotoxic chemotherapy, which was associated with a decrease in ex19del and disappearance of T790M and C797S; however, at disease progression, all EGFR mutations increased again in plasma together with MET amplification which was detected by NGS. Conclusions The measurement of ex19del changes in ctDNA is a simple and sensitive approach to monitor clinical outcome to osimertinib and, potentially, to other therapeutic interventions.
