Osimertinib may prolong progression-free survival (PFS) and has a strong overall response rate (ORR) in treatment-naive patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm), according to a study published in the Journal of Clinical Oncology.1

In spite of the initial effectiveness of EGFR-TKI therapies in patients with EGFRm advanced NSCLC, many patients develop acquired resistance and approximately 60% of these patients possess the EGFR T790M resistance mutation.

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Previously collected data from the Osimertinib First Time in Patients Ascending Dose (AURA) study (ClinicalTrials.gov Identifier: NCT01802632) demonstrated that osimertinib retains a high level of activity, delays resistance, and inhibits tumor growth in EGFRm tumors, and may be effective as first-line therapy for this patient population.

For this cohort of the AURA study, researchers assigned 60 treatment-naive patients to receive osimertinib 80 mg or 160 mg once daily, and blood samples were collected from patients whose disease progressed to assess osimertinib resistance mechanisms.

At a median follow-up of 19.1 months, patients in the 80 mg arm had an ORR of 67% (95% CI, 47%-83%) compared with 87% (95% CI, 69%-96%) for patients in the 160 mg arm.

Patients in the 80 mg arm achieved a median PFS of 22.1 months (95% CI, 13.7-30.2) compared with 19.3 months (95% CI, 13.7-26.0) for patients in the 160 mg arm.

Of the 38 patients who progressed after osimertinib treatment, 19 had no detectable levels of circulating tumor DNA (ctDNA). Nine of 19 patients with ctDNA had putative genomic resistance mechanisms, including amplifications of MET, EGFR and KRAS, and mutations such as MEK1, KRAS, PIK3CA, EGFRC797S, JAK2, and HER2 exon 20 insertions, but there was no evidence of acquired EGFR T790M resistance mutation for any of the study patients.

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According to the authors, the results of the study suggest that “osimertinib is an effective treatment approach as initial therapy for treatment-naive patients with advanced EGFR mutation-positive NSCLC.”


  1. Ramalingam SS, Yang J, Lee CK, et al. Osimertinib as first-line treatment of EGFR mutation–positive advanced non–small-cell lung cancer. J Clin Oncol. 2017 Aug 25. doi: 10.1200/JCO.2017.74.7576 [Epub ahead of print]