In a subgroup analysis from the phase III FLAURA2 trial reported in the Journal of Clinical Oncology, Pasi A. Jänne, MD, PhD, and colleagues found the combination of osimertinib and chemotherapy improved central nervous system (CNS) efficacy vs osimertinib alone in the first-line treatment of patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC).
FLAURA2 also showed that osimertinib/chemotherapy produced significantly longer progression-free survival vs osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC.
Pasi A. Jänne, MD, PhD
FLAURA2 Details
In the open-label trial, 557 patients were randomly assigned to receive osimertinib at 80 mg once daily plus pemetrexed at 500 mg/m2 with either cisplatin at 75 mg/m2 or carboplatin at AUC 5 on day 1 of 21-day cycles for four cycles, followed by osimertinib at 80 mg once daily and maintenance pemetrexed every 3 weeks (n = 279) or osimertinib at 80 mg once daily (n = 278).
Key Findings
On the basis of baseline CNS scans evaluated by a neuroradiologist through blinded independent central review, 118 patients in the combination group and 104 in the osimertinib monotherapy group had at least one measurable or nonmeasurable CNS lesion and were included in the CNS full-analysis set (cFAS); 40 and 38 patients, respectively, had at least one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response (cEFR) set.
In the cFAS, the hazard ratio for CNS progression or death for the combination vs monotherapy group was 0.58 (95% confidence interval [CI] = 0.33–1.01). Median CNS progression-free survival was 30.2 months vs 27.6 months; at 12 and 24 months, CNS progression-free survival was 87% vs 83% and 74% vs 54%, respectively.
In the cEFR set, the hazard ratio for CNS progression or death for the combination vs monotherapy group was 0.40 (95% CI = 0.19–0.84). At 12 and 24 months, CNS progression-free survival was 89% vs 73% and 65% vs 37%, respectively.
Among 161 vs 174 patients without baseline CNS metastases, the hazard ratio for CNS progression or death for the combination vs monotherapy group was 0.67 (95% CI = 0.43–1.04).
In the cFAS, CNS objective rates were 73% in the combination group vs 69% in the monotherapy group; CNS complete response was observed in 59% vs 43% of patients. In the cEFR set, CNS objective response rates were 88% vs 87%, with CNS complete response observed in 48% vs 16% of patients.
The investigators concluded, “Osimertinib plus platinum/pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.”
Dr. Jänne, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
