The EGFR tyrosine kinase inhibitor osimertinib showed promising efficacy and manageable toxicity in patients with advanced non–small-cell lung cancer (NSCLC) and central nervous system (CNS) metastases, according to a new study.
“Approximately 25% of patients with EGFR-mutated NSCLC present with CNS metastases at first diagnosis,” wrote study authors led by Glenwood Goss, MD, of the Ottawa Hospital Cancer Centre in Canada. The incidence of such metastases increases to more than 45% 3 years after diagnosis. “As patients are living longer, there is an increasing need for therapeutics that can ensure control within the sanctuary CNS site.”
The investigators analyzed pooled data from two phase II studies, the AURA and AURA2 trials. They included a total of 128 patients with CNS metastases on baseline scans, 50 of whom were eligible for the CNS response set. All patients had T790M-positive advanced NSCLC, and all had progressed following prior EGFR tyrosine kinase inhibitor therapy; they received osimertinib 80 mg once daily. The results were published in Annals of Oncology.
The confirmed CNS objective response rate was 54% (27 of 50 patients), with a median best percentage change from baseline in CNS target lesion size of −53%. The disease control rate in the CNS was 92%. Most responses were rapid, with 81% of responders showing a response by the time of the first assessment at 6 weeks.
The median CNS duration of response was not yet reached. At 3 months after onset of response, 100% of patients remained in response; at 6 months, 80% remained in response, and at 9 months, 75% remained. There was no correlation between CNS response and prior brain radiotherapy.
The median follow-up for CNS progression-free survival was 11 months among the 50 patients in the CNS response set. The median CNS progression-free survival was not reached, and 72% of patients remained progression-free at 6 months; at 12 months, 56% were progression-free. In total, 19 of the 50 patients experienced a progression event, and 12 patients (63%) had CNS progression, while 7 (37%) died in the absence of CNS progression.
The safety profile of osimertinib was consistent with that seen in the full patient populations of the two phase II trials. All patients experienced at least one adverse event, while grade 3 or worse events that were possibly caused by the study drug were seen in 12% of patients.
“Osimertinib demonstrated clinically meaningful efficacy in patients with CNS metastases,” the authors concluded. “Osimertinib offers an additional line of treatment for patients with T790M-positive NSCLC and CNS metastases.”