Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.