New-age AURA.

Top Line: Osimertinib has more intracranial activity than standard chemo, so let’s see how it stacks up against other EGFR-TKIs.
The Study: In non-small cell lung cancer (NSCLC), the ALK-TKI alectinib has demonstrated significant intracranial activity. Not to be outdone, the rising star ofEGFR-TKIs, osimertinib, also appeared to show promising intracranial activity compared to chemo in a subset analysis of the AURA3 trial. Now we have another pre-planned sub-analysis of patients with brain metastases, this time from the FLAURA trial where osimertinib shined against gefitinib and erlotinib as first-line therapy for advanced EGFR-mutated NSCLC. While the trial enrolled over 500 patients, only around 200 had baseline brain imaging, required only for patients with known or suspected brain mets at enrollment. An important detail is the definition of “measurable” disease, which had to be at least 1 cm or 2x the thickness of MRI slices. So we end up with 128 patients with brain lesions but only 41 with “measurable” disease. Nearly 75% of patients had 1-3 brain metastases, and roughly 25% had received prior brain radiation. Compared to standard EGFR-TKIs, osimertinib significantly prolonged intracranial progression free survival and halved the rate of intracranial progression. Response rate was also improved from  43 → 66% overall and 68→ 91% in those with measurable disease. In AURA3, patients with prior radiotherapy had better response rates, but FLAURA didn’t go there.
Bottom Line: Osimertinib has more intracranial activity and lower rates of intracranial progression than other EGFR-TKIs such as gefitinib and erlotinib. | Reungwetwattana, J Clin Oncol 2018


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