Аннотация:PURPOSE We report CNS efficacy of first-line osimertinib plus chemotherapy versusosimertinib monotherapy in patients with epidermal growth factor receptor(EGFR)–mutated advanced non–small-cell lung cancer (NSCLC) from the phaseIII FLAURA2 study according to baseline CNS metastasis status.METHODS Patients were randomly assigned to osimertinib plus platinum-pemetrexed(combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients withbaseline CNS metastases; scans were assessed by neuroradiologist CNS blindedindependent central review (BICR).RESULTS On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278(monotherapy) randomly assigned patients had ≥one measurable and/ornonmeasurable CNS lesion and were included in the CNS full analysis set(cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion andwere included in the post hoc CNS evaluable-for-response set (cEFR). In thecFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI,0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNSprogression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objectiveresponse rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69%(monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). Inthe cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48%versus 16% had CNS CR.CONCLUSION Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacycompared 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 advancedNSCLC, including those with CNS metastases.