Aumolertinib shows promise in untreated EGFR-variant metastatic NSCLC

High-dose aumolertinib appears to provide progression-free survival (PFS) benefit to patients with untreated EGFR-variant non–small cell lung cancer (NSCLC) and brain metastases, while having a manageable safety profile, according to the results of a single-arm phase II study.

The study was conducted at 10 sites in China and included 63 patients (median age 60 years, 61.9 percent female). These patients received treatment with aumolertinib at a dose of 165 mg, taken orally once daily in each 28-day cycle until disease progression or unacceptable toxic effects.

The primary endpoint of 12-month PFS rate was assessed by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

All 63 patients were included in the full analysis set. A subset of 49 patients who had at least one measurable brain lesion were included in the CNS evaluable-for-response set. The median follow-up duration was 28.8 months.

In the full analysis set, the 12-month PFS rate was 62.1 percent (95 percent confidence interval [CI], 48.7–73.0), and the 12-month intracranial PFS rate was 76.8 percent (95 percent CI, 63.2–85.9). The median PFS was 20.5 months (95 percent CI, 12.0–26.9), while the median intracranial PFS and overall survival were not reached.

The percentage of patients with systemic and intracranial objective response per RECIST 1.1 was 88.9 percent (95 percent CI, 78.4–95.4) and 82.5 percent (95 percent CI, 70.9–90.9) in the full analysis set and 87.8 percent (95 percent CI, 75.2–95.4) and 85.7 percent (95 percent CI, 72.8–94.1) in the CNS evaluable-for-response set, respectively.

In terms of safety, blood creatine phosphokinase was the most common grade 3 or 4 treatment-related adverse event, occurring in 27.0 percent of patients. There were no incidences of treatment-related deaths.

EGFR variant clearance in plasma circulating tumour DNA at day 1 of cycle 2 was predictive of longer PFS (hazard ratio, 0.14, 95 percent CI, 0.04–0.47; p=0.001).