Osimertinib in First-Line Treatment of EGFR Mutation–Positive Advanced NSCLC

Key Points

  • Among all patients with previously untreated EGFR mutation–positive advanced NSCLC, the response rate to osimertinib was 77%, and median progression-free survival was 20.5 months.
  • No evidence of acquired EGFR T790M mutation was observed.

Osimertinib (Tagrisso) has shown high activity in the phase I expansion component of the AURA trial in previously untreated patients with EGFR mutation–positive advanced non–small cell lung cancer (NSCLC). These findings were reported by Ramalingam et al in the Journal of Clinical Oncology.

Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) selective for EGFR-TKI–sensitizing (EGFRm) and EGFR T790M resistance mutations. It is currently approved for the treatment of metastatic EGFR T790M–positive NSCLC after progression on or after EGFR-TKI therapy.

Study Details

In the study, 60 patients with locally advanced or metastatic EGFRm disease received osimertinib at 80 (n = 30) or 160 mg (n = 30) once daily. The study endpoints included investigator-assessed objective response rate and progression-free survival. Plasma samples were collected at or after disease progression to assess potential osimertinib resistance mechanisms.

Responses and Progression-Free Survival

Median follow-up at data cutoff in November 2016 was 19.1 months. Response rates were 77% among all patients, 67% in the 80-mg group, and 87% in the 160-mg group. Overall disease control rates were 97%, 93%, and 100%, respectively. Median duration of response was 18.0, 19.3, and 16.7 months, respectively. Median progression-free survival was 20.5, 22.1, and 19.3 months, respectively.

Among 38 patients with post–disease progression plasma samples, 19 (50%) had no detectable circulating tumor DNA. Potential resistance mechanisms were identified in 9 of the other 19 patients, including MET amplification (n = 1); EGFR and KRAS amplification (n = 1); MEK1, KRAS, or PIK3CA mutation (n = 1 each); EGFR C797S mutation (n = 2); JAK2 mutation (n = 1); and HER2 exon 20 insertion (n = 1). No acquired EGFR T790M was detected.

Adverse Events

Grade ≥ 3 adverse events occurred in 60% of the 80-mg group and 63% of the 160-mg group, with 13% and 23% considered possibly related to treatment. Serious adverse events occurred in 47% and 30%, with 13% and 3% considered related to treatment. Adverse events led to treatment discontinuation in 10% of each group.

The investigators concluded: “Osimertinib demonstrated a robust [objective response rate] and prolonged [progression-free survival] in treatment-naive patients with EGFRm advanced NSCLC. There was no evidence of acquired EGFR T790M mutation in post-progression plasma samples.”

The study was supported by AstraZeneca.

Suresh S. Ramalingam, MD, of Emory University School of Medicine, Winship Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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