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ERBB Mutation as Predictive Biomarker for Afatinib Treatment in Lung Cancer

By: Andrew Goldstein
Posted: Wednesday, August 29, 2018

Patients who have squamous non–small cell lung cancer (NSCLC) with ERBB family mutations had better outcomes when treated with afatinib than those who did not have these mutations, according to a genetic secondary analysis of patients in the LUX-Lung 8 trial published in JAMA Oncology. Glenwood D. Goss, MD, of The Ottawa Hospital Research Institute, Ontario, Canada, and colleagues propose that next-generation sequencing may help identify patients with lung squamous cell carcinoma who may reap additional benefit from afatinib treatment.

In the LUX-Lung 8 trial, 795 patients with stage IIIB or IV squamous NSCLC that had progressed after 4 or more cycles of platinum-based doublet chemotherapy were randomized to receive treatment with afatinib or erlotinib. Patients treated with afatinib had significantly improved overall survival, hazard ratios, and progression-free survival than those treated with erlotinib.

Tumor specimens from 245 of these patients with progression-free survival of more than 2 months—132 patients treated with afatinib and 113 with erlotinib—underwent genetic analysis. In all, 53 of the 245 patients had tumors with at least 1 ERBB family mutation.

Dr. Goss and colleagues found that ERBB mutation–positive patients had longer median progression-free survival, 4.9 months, and median overall survival, 10.6 months, than those without, this mutation—whose median overall survival and progression-free survival was 3.0 months and 8.1 months, respectively. The largest benefits were reported in patients with HER2 or HER4 mutations.

“We hypothesize that the additional benefit with afatinib is attributable to its broad, irreversible inhibition of the entire ERBB signaling network,” the authors concluded.



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