Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m² ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).

Keywords: Japanese; epidermal growth factor receptor; mutation; non-small-cell lung cancer; tyrosine kinase.

Figure 1

Patient disposition in the Japanese subgroup of patients with EGFR T790M mutation‐positive advanced non‐small‐cell lung cancer treated with osimertinib or platinum‐pemetrexed therapy. Patients in the platinum‐pemetrexed group were counted only if they discontinued all platinum‐pemetrexed treatment. If a patient discontinued platinum‐pemetrexed treatments at different times during the trial, they were counted under the last recorded reason for discontinuation of platinum‐pemetrexed. If a patient discontinued platinum‐pemetrexed treatments at the same time, the patient was counted under a single reason using the following order: adverse event, objective disease progression, severe protocol non‐compliance, lost to follow‐up, patient decision, maximum cycle of platinum‐pemetrexed reached, or other

Figure 2

Progression‐free survival (PFS) using investigator assessment in all patients21 (A) and Japanese patients (B) enrolled with EGFR T790M mutation‐positive advanced non‐small‐cell lung cancer treated with either osimertinib or platinum‐pemetrexed therapy. A, In all patients, the median PFS was 10.1 mo (95% confidence interval [CI], 8.3‐12.3) in the osimertinib group and 4.4 (95% CI, 4.2‐5.6) in the platinum‐pemetrexed group (hazard ratio, 0.30; 95% CI, 0.23‐0.41; P < 0.001). B, In the Japanese patients, the median PFS was 12.5 mo (95% CI, 6.9‐not calculated) in the osimertinib group and 4.3 (95% CI, 4.0‐6.7) in the platinum‐pemetrexed group (hazard ratio, 0.27; 95% CI, 0.13‐0.56)