CNS efficacy of osimertinib plus chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer

A recent study showed that the combination of osimertinib with platinum-pemetrexed exhibited improved central nervous system (CNS) efficacy when compared to osimertinib monotherapy. This study’s findings were published in the Journal of clinical oncology. 

In the phase 3 FLAURA2 trial, patients were assigned randomly to receive either osimertinib with platinum-pemetrexed (n= 279) or osimertinib monotherapy (n=278) until disease progression or discontinuation. Brain scans were conducted for all patients at the baseline and upon progression, as well as at scheduled evaluations until progression for those with baseline CNS metastases. The scans were evaluated by a neuroradiologist through a CNS blinded independent central review (BICR).

Based on the baseline CNS BICR, a total of 118 out of 279 patients in the combination group and 104 out of 278 patients in the monotherapy group were included in the CNS full analysis set (cFAS) due to having ≥ one measurable and/or nonmeasurable CNS lesion. Among them, 40 patients from the combination group and 38 patients from the monotherapy group had ≥ one measurable target CNS lesion and were part of the post hoc CNS evaluable-for-response set (cEFR). The hazard ratio (HR) for CNS progression or death was 0.58 in the cFAS , while it was 0.67 for patients who did not have CNS metastases at baseline. The CNS objective response rates in the cFAS were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78), with 59% versus 43% achieving CNS complete response (CR). In the cEFR, CNS ORRs were 88% (73 to 96) versus 87% (72 to 96), with 48% versus 16% achieving CNS CR.

Thus, it can be concluded that the combination of osimertinib and platinum-pemetrexed demonstrated enhanced CNS efficacy compared to osimertinib alone. Additionally, this combination therapy may delay CNS progression, regardless of the baseline CNS metastasis status. These findings strongly support the use of this treatment as a new first-line approach for patients diagnosed with EGFR-mutated advanced non-small cell lung cancer (NSCLC), including those with CNS metastases.