All in your head.

Top Line: Intracranial failures are increasing in the era of targeted therapies, whose successes outside the brain often outpace activity within the...dun dun dun...notorious blood brain barrier.
The Study: Last year, the phase 3 AURA3 trial reported a survival advantage with the EGFR-targeted agent osimertinib over standard platinum/pemetrexed chemo in patients with non-small cell lung cancer (NSCLC) with EGFR-T790M mutations who failed a first-line EGFR-TKI. But if that’s not a specific enough patient population for ya, here’s a pre-planned subgroup analysis specifically on the enrollees with brain mets, which ended up being 116 of the 419 originals. Of note, brain mets were only allowed if “stable” and asymptomatic without steroids. Median times to brain failure or death with osimertinib and chemo were 12 and 6 months, respectively. Overall, rates of objective response (OR) / median duration of response were 40% / 9 months with osimertinib and only 17% / 6 months with chemo. Even more impressive were the rates of OR among the 46 patients with “measurable” (>1 cm) brain mets: 70% with osimertinib and 31% with chemo. How does this change clinical practice? Not a ton considering patients with EGFR-T790M mutant NSCLC already have indications for osimertinib regardless of brain mets. And when considering whether this supports omission of radiation, consider this: those receiving brain radiation within 6 months prior to osimertinib had the highest response rate of all at 9/14 (64%) versus 21/61 (34%) without recent radiation.
Bottom Line: With osimertinib, EGFR-TKIs can officially join the ranks of ALK-TKIs as targeted therapies with demonstrated intracranial activity. But it likely adds to, rather than replaces, the role of cranial radiation. | Wu, J CLin Oncol 2018


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