Nimit Singhal1, Sina Vatandoust, Michael P Brown. 1. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia, Nimit.Singhal@health.sa.gov.au.
Abstract
INTRODUCTION: Lung cancer is one of the most common malignancies worldwide. Non-small cell lung cancer (NSCLC) comprises the majority of the cases of lung cancer. Previous studies have demonstrated a role for both the estrogen pathway and mammalian target of rapamycin (mTOR) in NSCLC. METHODS: This single-arm phase 2 study was designed to assess the safety and efficacy of combination treatment with aromatase inhibitor—letrozole—and mTOR inhibitor—everolimus—in the treatment of patients with advanced (unresectable stage III or stage IV) NSCLC who had failed at least one line of platinum-based chemotherapy. RESULTS: The study was closed after enrolling five patients due to safety concerns. Of the five patients treated with the study combination, two patients developed grade 5 pulmonary toxicity and another patient developed reversible grade 4 pulmonary toxicity. CONCLUSIONS: There is a probable causal relationship between the study medication and the reported serious adverse events. In the absence of additional clinical data in lung cancer patients, we recommend that extreme caution be exercised in the use of combined letrozole and everolimus regimens in patients with advanced lung cancers, active pulmonary pathologies, or both.
INTRODUCTION:Lung cancer is one of the most common malignancies worldwide. Non-small cell lung cancer (NSCLC) comprises the majority of the cases of lung cancer. Previous studies have demonstrated a role for both the estrogen pathway and mammalian target of rapamycin (mTOR) in NSCLC. METHODS: This single-arm phase 2 study was designed to assess the safety and efficacy of combination treatment with aromatase inhibitor—letrozole—and mTOR inhibitor—everolimus—in the treatment of patients with advanced (unresectable stage III or stage IV) NSCLC who had failed at least one line of platinum-based chemotherapy. RESULTS: The study was closed after enrolling five patients due to safety concerns. Of the five patients treated with the study combination, two patients developed grade 5 pulmonary toxicity and another patient developed reversible grade 4 pulmonary toxicity. CONCLUSIONS: There is a probable causal relationship between the study medication and the reported serious adverse events. In the absence of additional clinical data in lung cancerpatients, we recommend that extreme caution be exercised in the use of combined letrozole and everolimus regimens in patients with advanced lung cancers, active pulmonary pathologies, or both.
Authors: Gonda Konings; Linda Brentjens; Bert Delvoux; Tero Linnanen; Karlijn Cornel; Pasi Koskimies; Marlies Bongers; Roy Kruitwagen; Sofia Xanthoulea; Andrea Romano Journal: Front Pharmacol Date: 2018-09-19 Impact factor: 5.810