Osimertinib may be more effective against central nervous system (CNS) metastases among patients with T790M-positive advanced non-small cell lung cancer (NSCLC) compared with platinum-based chemotherapy plus pemetrexed, according to a study published in the Journal of Clinical Oncology.1
CNS metastases are commonly observed in NSCLC, with nearly a 50% incidence rate over the course of disease. Many treatments, including first- and second-generation tyrosine kinase inhibitors (TKI) and chemotherapies, have been unable to effectively cross the blood-brain barrier (BBB), leaving an unmet need in this patient population. Previous studies have demonstrated that osimertinib may have potential to improve outcomes among patients with CNS metastases.
For this preplanned subgroup analysis of the AURA3 phase 3 (ClinicalTrials.gov Identifier: NCT02151981) study, researchers randomly assigned 116 patients with EGFR T790M-positive NSCLC and CNS lesions to receive osimertinib or platinum (carboplatin or cisplatin) plus pemetrexed. Eligible patients had progressed with first-line EGFR-TKI therapy, were asymptomatic/stable, and did not require steroids for at least 4 weeks prior to study initiation.
At time of data cutoff, the CNS overall response rate (ORR) among patients with 1 or more measureable CNS lesions (≥ 10 mm in the longest diameter) treated with osimertinib was 70% (21 of 30; 95% CI, 51%-85%) compared with 31% (5 of 16; 95% CI, 11%-59%) among those who received platinum-pemetrexed (odds ratio, 5.13; 95% CI, 1.44-20.64; P = .015).
Among patients with non-measurable and/or measurable CNS legions, the ORR was 40% (30 of 75; 95% CI, 29%-52%) and 17% (7 of 41; 95% CI, 7%-32%) among patients treated with osimertinib and platinum-pemetrexed, respectively (OR, 3.24; 95% CI, 1.33-8.81; P = .014).
The median CNS duration of response among patients with measurable and/or non-measurable CNS lesions was 8.9 months (95% CI, 4.3-not evaluable) for the osimertinib arm compared with 5.7 months (95% CI, 4.4-5.7) for the platinum-pemetrexed arm. The median CNS progression-free survival was 11.7 months for the osimertinib arm and 5.6 months for the platinum-pemetrexed arm (hazard ratio, 0.32; 95% CI, 0.15-0.69; P = .004).
The authors concluded that “the consistent efficacy across CNS analyses in the phase 2 and phase 3 studies indicates that osimertinib offers robust and durable efficacy against CNS metastases in patients with T790M-positive NSCLC and disease progression with first-line EGFR-TKI, an area of high unmet medical need.”
- Wu YL, Ahn MJ, Garassino MC, et al. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3) [published online July 30, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.77.9363