title: Unexpected responses to EGFR inhibition in NSCLC.
abstract: The presence of activating mutations of the epidermal growth factor receptor (EGFR)-gene identifies a distinct and clinically relevant molecular subset of non-small-cell lung cancer. It is now well demonstrated that EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are superior to standard chemotherapy in this subset of tumors. Nevertheless, in many cases, responses are not durable and last for 6-12 months due to the occurrence of secondary or acquired resistance. Here we present three cases of EGFR-mutant lung adenocarcinomas (ADC), that showed an unexpected response to anti-EGFR small molecules. The first patient presented a continued 89 month-long response to erlotinib in a tumor recurred after surgery and conventional chemotherapy. In the other cases, subclinically persistent tumor in the lung tissue was documented histologically in lung resections performed after partial response to TKI treatment. The persistence of interstitial and endolymphatic tumor cells after TKI treatment might explain the common observation of tumor relapse after TKI discontinuation, and sustain the decision to continue treatment in responsive patients as in our first case.
authors.affiliation: Department of Molecular Medicine, Laboratory of Biochemistry and Genetics, Pneumology Unit, University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Stella
authors.affiliation: Department of Molecular Medicine, Laboratory of Biochemistry and Genetics, Pneumology Unit, University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Valizia
authors.affiliation: Department of Molecular Medicine, Laboratory of Biochemistry and Genetics, Pneumology Unit, University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.affiliation: Department of Molecular Medicine, Laboratory of Biochemistry and Genetics, Pneumology Unit, University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Inghilleri
authors.affiliation: Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Valentini
authors.affiliation: Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Dore
authors.affiliation: Department of Hemato-oncology, Radiation Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Colombo
authors.affiliation: Department of Hemato-oncology, Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Valentino
authors.affiliation: Cardiothoracic Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Orlandoni
authors.affiliation: Department of Molecular Medicine, Section of Pathology, University of Pavia and Foundation IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morbini
keywords: Actionable markers; Cancer genetics; Targeted therapy