Long-Term Data Confirm Osimertinib as Standard of Care for T790M-Positive NSCLC

Long-term follow-up data from a pooled analysis of 2 clinical trials underscore the steadfast role of osimertinib as standard of care in patients with advanced non–small-cell lung cancer (NSCLC) and T790M mutations (Cancer. 2018 Dec 4. Epub ahead of print).

The analysis, conducted by Myung-Ju Ahn, MD, Section of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues, has been the most comprehensive and lengthy study of osimertinib use in this patient population.

“Osimertinib is a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR‐TKI–sensitizing and T790M (threonine‐to‐methionine substitution at codon 790)‐resistance mutations,” they explained.

Data from a 2017 phase 3 trial demonstrated osimertinib’s role in improving response rates and progression-free survival (PFS) in patients with advanced NSCLC and T790M mutations versus platinum-based chemotherapy. Dr Ahn and colleagues, however, performed their analysis using data from the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial and the AURA2 trial (NCT02094261), both phase 2 studies.

Patients received osimertinib for a median of 16.4 months; they had a median age of 63 years, approximately 70% were women, and the majority were never-smokers (72%). At baseline, 96% of patients had metastatic disease whereas the other 4% had locally advanced disease.

In total, 398 patients were deemed evaluable. Of these patients, 262 (66%) had objective responses. The median time to response was 5.9 weeks, and the median duration of response was 12.3 months. Approximately 80% of patients were still responding to the therapy at 6 months. At 9 and 12 months, the response rates were 63% and 51%, respectively.

With regard to PFS, at a median of 8.3 months (when Dr Ahn and colleagues carried out an updated data cutoff) 63% of patients had disease progression. The median PFS was 9.9 months, and at 6, 12, and 24 months, 70%, 46%, and 24% of patients were still alive and free from disease progression, respectively.

According to Dr Ahn and colleagues, the median overall survival (OS) was 26.8 months. In addition, OS rates were 80%, 55%, and 37% at 12, 24, and 36 months, respectively.

Decreased neutrophil count, neutropenia, and increased alanine aminotransferase were among the most common adverse events associated with osimertinib use in these patients. Almost all patients had at least 1 adverse event, but most were mild in severity; adverse events grade ≥3 occurred in 16%.

“This pooled analysis represents the most mature clinical trial data for osimertinib in patients with pretreated, T790M-positive, advanced non-small cell lung cancer, further establishing osimertinib as a standard of care for this patient population,” Dr Ahn and colleagues concluded.—Hina Khaliq