The long-term results from an analysis of two phase II studies confirmed the role of osimertinib in the treatment of T790M mutation–positive advanced non–small-cell lung cancer.
The long-term results from a pooled analysis of two phase II studies confirmed the role of osimertinib in the treatment of patients with T790M mutation–positive advanced non–small-cell lung cancer (NSCLC). Though the extended results came as no surprise, the analysis represents the longest follow-up for the drug in this patient population to date.
“In the treatment of EGFR-mutated NSCLC, first-line therapy with EGFR tyrosine kinase inhibitors (TKIs) is associated with high response rates, although most patients eventually develop treatment-resistant disease,” wrote study authors led by Myung-Ju Ahn, MD, of Samsung Medical Center in Seoul. “Greater than 50% of patients with acquired resistance to EGFR TKIs have detectable EGFR T790M resistance mutations.”
Previous research including a phase III trial showed that the third-generation EGFR TKI osimertinib improves response rates and progression-free survival (PFS) over platinum-pemetrexed in patients with T790M mutations. In the new analysis, researchers reported the long-term results from 411 patients enrolled in the AURA and AURA2 phase II trials. The results were published in Cancer.
The median age in the pooled analysis was 63 years, and 68% of the cohort were women. Most patients (72%) had never smoked; 96% had metastatic disease at baseline, and 4% had locally advanced disease.
The median duration of treatment with osimertinib was 16.4 months. The objective response rate was 66% (262 of 398 evaluable patients). The median duration of response was 12.3 months, and 77% of patients had an ongoing response at 6 months. That rate was 63% at 9 months, and 51% at 12 months following study entry. The median time to response was 5.9 weeks.
An updated data cutoff occurred after a median follow-up for PFS of 8.3 months; at that point, 63% had disease progression. The median PFS was 9.9 months, and 70% of patients were alive and free from progression at 6 months. At 12 months, that rate was 46%, and at 24 months it was 24%. The median PFS among patients with a history of central nervous system metastases was 8.2 months, compared with 12.4 months in those with no such history.
The median overall survival in the pooled analysis was 26.8 months. The overall survival rates at 12 months, 24 months, and 36 months were 80%, 55%, and 37%, respectively.
Though most patients reported at least one adverse event (99%), most of these were mild in severity; grade 3 or higher adverse events were reported in 16% of the cohort. The most common adverse events included decreased neutrophil count (2%), neutropenia (2%), and increased alanine aminotransferase (1%). The authors noted that no new safety signals have emerged since the last analysis.
Heather Wakelee, MD, of Stanford University Medical Center, who was not involved in the research, said there are “no real surprises here, but it is good to have the longer-term follow-up data published from these studies.” She added that these results confirm the role of osimertinib in patients with T790M mutations who have progressed on a first-generation EGFR TKI. “However,” she said, “as osimertinib moves more into the first-line setting, this will be less relevant.”