SESSION TYPE: Cancer Student/Resident Cases
PRESENTED ON: Monday, October 22, 2012 at 01:45 PM - 03:00 PM
INTRODUCTION: Non-small cell lung cancer (NSCLC) cells have marked genetic heterogeneity. Patients with activating mutations of the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene constitute a third of lung adenocarcinomas in never/light smokers. Erlotinib, an oral EGFR inhibitor (ETKI), targets this oncogenic dependence by suppressing EGFR mutation positive clones (ETKI sensitive). However, to date there is no curative regimen due to genotypic-phenotypic adaptations.
CASE PRESENTATION: A 70 year old non-smoker Caucasian male was found in May 2009 with stage IV lung adenocarcinoma, bilateral pulmonary metastases (since May 2008), worsening dyspnea on exertion (DOE) and fatigue. Disease progressed after first-line systemic chemotherapy. Twice he had a significant tumor response on CT scan followed by tumor progression on ETKI, after an “erlotinib-free interval”. In December 2011, he was re-challenged a third time with 150mg of oral erlotinib. His DOE and fatigue resolved within a week of treatment. Furthermore an interval reduction in right upper lobe and left lower lobe masses with resolution of the bilateral pulmonary nodules were noted in February 2012. He continues on erlotinib. Please refer to table 1 illustrating the course of treatment.
DISCUSSION: Acquired resistance to TKI is tumor progression after an initial objective tumor response to ETKI treatment fulfilling the RECIST criteria. Re-biopsy may help classify the resistance pattern. Resistance is possibly through a clonal selection that favors the perpetuation of the “gatekeeper” mutant, ETKI-resistant T790M clones, which may or may not be present at diagnosis. Biologically, this mutation is associated with a more indolent course and disease progression within a previously involved organ system. We illustrate ecological principles in cancer evolution in this case of acquired resistance and response to re-treatment following an “erlotinib-free interval”, which renders the more indolent ETKI resistant clones to be overcome by the proliferation of the more efficient TKI-sensitive clone in the absence of erlotinib suppression. Thus, there is sensitivity to erlotinib re-treatment upon disease progression during the ‘erlotinib-free interval’.
CONCLUSIONS: This case demonstrates ecological dynamics in lung adenocarcinoma underlying treatment sensitivity to erlotinib re-challenge despite documented acquired resistance.The role of erlotinib as continued maintenance erlotinib therapy for NSCLC in these cases should be further investigated.
1) Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. Science Translational Medicine 2011;3.
2) Becker A, Crombag L, Heideman DAM, et al. Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. European Journal of Cancer 2011;47:2603-6.
DISCLOSURE: The following authors have nothing to disclose: Tushar Chopra, Grace Dy, Nazneen Tata
No Product/Research Disclosure InformationState University of New York at Buffalo, Buffalo, NY