Molecular testing is recommended for initial diagnosis in patients with non–small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging “actionable” targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences.
Kevin S. Scher, Juan-Sebastian Saldivar, Michael Fishbein, Alberto Marchevsky, and Karen L. Reckamp
This case report describes the rare occurrence of a T790M resistance mutation found in a central nervous system (CNS) parenchymal metastasis. A concomitant squamous histology transformation in a lung non-T790M-resistant metastasis is also described. The authors hypothesize that this CNS resistance and histology transformation may have resulted from intermittent use of erlotinib treatment. This case report emphasizes the complexities of using erlotinib in the induction setting.
Robert A. Figlin, Elizabeth Brown, Andrew J. Armstrong, Wallace Akerley, Al B. Benson III, Harold J. Burstein, David S. Ettinger, Phillip G. Febbo, Matthew G. Fury, Gary R. Hudes, Merrill S. Kies, Eunice L. Kwak, Robert J. Morgan Jr., Joanne Mortimer, Karen Reckamp, Alan P. Venook, Frank Worden, and Yun Yen
The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors. (JNCCN 2008;6[Suppl 5]:S1—S20)