“Among the notable updates in the National Comprehensive Cancer Network’s (NCCN) recently released treatment guidelines for non–small cell cancer (NSCLC) is the category 2A recommendation to give osimertinib (Tagrisso), a third-generation irreversible EGFR inhibitor designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, in the first-line setting for patients whose disease is EGFR mutant, explains Suresh A. Ramalingam, MD.
“Osimertinib was also given a category 1 recommendation as a subsequent therapy after patients progressed on treatment with standard EGFR tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif). The FDA granted a breakthrough therapy designation to a supplemental biologics license application for osimertinib as a frontline treatment for patients with metastatic EGFR-mutation–positive NSCLC in October 2017. The application was based on findings from the double-blind, phase III FLAURA trial, in which frontline osimertinib was associated with a 54% reduction in the risk of progression or death compared with standard therapy.”
“The combination of osimertinib (Tagrisso) and the MET inhibitor savolitinib showed signs of efficacy for pretreated patients with MET-positive, EGFR-mutant non–small cell lung cancer (NSCLC), regardless of prior treatment with a T790M-directed therapy, according to findings from part B of the TATTON trial presented at the 2017 World Conference on Lung Cancer (WCLC).
“Across patients in the phase Ib study (N = 64), the objective response rate (ORR) was 47% with the combination of osimertinib and savolitinib. In those pretreated with a T790M-directed therapy (n = 30), the ORR was 33% and in those with T790M-negative disease (n = 23) the ORR was 61%. In patients with T790M-positive disease (n = 11), the ORR was 55% for the combination.”
“Osimertinib improves progression-free survival by 54% compared to standard first line therapy in patients with EGFR mutated non-small-cell lung cancer (NSCLC), according to late-breaking results from the FLAURA trial presented today at the ESMO 2017 Congress in Madrid.
“EGFR mutations are present in around 15% of NSCLC in Western populations, rising to 35% in Asian populations. EGFR inhibitors are superior to chemotherapy in the first line treatment of these patients. However, despite high response rates and good progression-free survival, patients invariably develop resistance to drugs such as erlotinib and gefitinib. In the majority of patients this resistance is mediated by a T790M mutation.”
Medical guidelines for treatment of newly diagnosed non-small cell lung cancer (NSCLC) mandate upfront testing of tumor tissue for mutations in the EGFR gene (as well as ALK and ROS gene translocation). EGFR mutations are found in 10 to 15% of white patients, but in patients of East Asian origin such mutations are in encountered in approximately 48%. However, with new data and drugs entering the playing field, newly diagnosed patients’ treatment decisions could become more complex.
There is a good reason to test for EGFR mutations: the accumulated data show that, compared to first-line chemotherapy, treatment with drugs that inhibit the activity of EGFR in patients with activating EGFR mutations improves patients’ median progression-free survival (PFS) time from 4.6 to 6.9 months to 9.6 to 13.1 months, and has a higher objective response rate (ORR). Moreover, EGFR inhibitors are associated with a significantly lower incidence of adverse effects and better control of disease symptoms. Continue reading…
“AstraZeneca has presented new data showing that Tagrisso also extends progression-free survival for non-small cell lung cancer (NSCLC) patients who have central nervous system (CNS) metastases.
“According to findings from the AURA3 trial, patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC given the drug lived without disease worsening or death for 11.7 months compared to 5.6 months for those receiving chemotherapy.”
“The China Food and Drug Administration (CFDA) has approved osimertinib for the treatment of patients with locally-advanced or metastatic EGFR T790M-positive non–small cell lung cancer (NSCLC) with progression following treatment with an EGFR tyrosine kinase inhibitor (TKI).
“Osimertinib was approved under the CFDA’s accelerated Priority Review Pathway. To receive the treatment, patients must have their EGFR T790M mutation status confirmed through a validated test.”
“Genprex, Inc. today announced positive interim data from an ongoing Phase II clinical trial (NCT01455389) evaluating its investigational immunogene therapy candidate Oncoprex™ in combination with the tyrosine kinase inhibitor (TKI) erlotinib (Tarceva®) for the treatment of late stage non-small cell lung cancer (NSCLC) patients.”
“AstraZeneca today presented data from the AURA3 trial that data is supportive of Tagrisso (osimertinib) potentially becoming the new standard of care for 2nd-line treatment of patients with epidermal growth factor receptor (EGFR) T790M mutation-positive locally-advanced or metastatic non-small cell lung cancer (NSCLC). The first randomised Phase III data showed that Tagrisso 2nd-line therapy improved progression-free survival (PFS) by 5.7 months compared with standard platinum-based doublet chemotherapy (Hazard Ratio [HR]=0.3). The results were presented at the 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, hosted by the International Association for the Study of Lung Cancer, and published simultaneously online in The New England Journal of Medicine.”
“Combined results from subset analyses of the TIGER-X and TIGER-2 clinical trials show that the VeriStrat test stratifies T790M-mutated patients with previously-treated, advanced non-small cell lung cancer (NSCLC) who are more or less likely to experience longer progression-free survival (PFS) when treated with a third-generation EGFR-TKI therapy. Clinical trial data suggesting the test’s potential for identifying better candidates for third-generation EGFR-TKI therapy were presented in Chicago last Friday at the at the IASLC Multidisciplinary Symposium in Thoracic Oncology hosted by the International Association for the Study of Lung Cancer.”