Novel agents in development for advanced non-small cell lung cancer

Abstract

Abstract:The identification of EGFR mutations and ALK rearrangements in nonsmall cell lung cancer (NSCLC) has led to the rapid development of targeted therapies and significant changes in the treatment paradigm. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and crizotinib are now standard therapies for patients with the appropriate molecular alteration. Current investigations are determining the mechanisms of resistance to targeted therapies and developing novel agents to combat resistance. For patients with KRAS mutant NSCLC, a phase III trial of the MEK inhibitor, selumetinib, has been initiated. For patients without a defined mutation or a mutation without a known targeted therapy, immunotherapy, ganetespib, nintedanib and MET inhibitors in combination with EGFR TKIs are in development. Preliminary results of phase III trials raise doubts about the future development of dacomitinib as a second-line agent.

Enumeration and Molecular Characterization of Tumor Cells in Lung Cancer Patients Using a Novel In Vivo Device for Capturing Circulating Tumor Cells

“…Besides monitoring of response to therapy, the molecular characterization of CTCs can provide important information on therapeutic targets or resistance mechanisms (23)(24)(25)(26)(27)(28). Thus, we evaluated whether the in vivo isolated CTCs also allow subsequent molecular characterization of genes relevant to therapy of cancer patients.…”

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…In addition, the objective response rate was improved with osimertinib (71%; 95% CI, 65%-76%) compared with chemotherapy (31%; 95% CI, 24%-40%) ( [90][91][92][93][94][95][96][97][98] in patients with EGFR T790M whose disease has progressed on sensitizing EGFR TKI therapy; 13% (33/253) of patients had drug-related grade ≥3 AEs with 1 fatal event from pneumonia possibly related to treatment. 39,160,161 In patients without EGFR T790M, the response rate was 21% (13/61; 95% CI, 12-34) and the PFS was 2.8 months (95% CI, 2.1-4.3).…”

“…[94][95][96][97][98][99][100][101][102][103][104] Ceritinib is an orally active TKI of ALK, which also inhibits the insulin-like growth factor 1 (IGF-1) receptor but not MET. An expanded phase I trial showed that ceritinib was very active in 122 patients with locally advanced or metastatic NSCLC who have ALK gene rearrangements.…”

“…133,136 Targeted therapy is not currently available for patients with KRAS mutations, although immune checkpoint inhibitors appear to be effective; MEK inhibitors are in clinical trials. 97,127,137,138 Targeted Therapies Specific targeted therapies are available for the treatment of advanced NSCLC. [139][140][141] Erlotinib, gefitinib, and afatinib are small molecule inhibitors of EGFR; osimertinib targets T790M.…”

Lung Cancer Treatment: Status 2015

“…No agents are approved for this cohort to the date, there is a phase II trial on Selumetinib that has shown some benefit, and phase 3 is on the way. And there are some less frequent mutations, and their practical use in treatment of lung cancer is to the date not clear [9] (Figure 1). We know we can use some of the as a target, but I believe that we'll get to know much more about these oncogenes too in the nearest future.…”