The times they are a changin’.

Top Line: Let’s revisit the bold conclusion posed by the Australian phase 2 trial upon showing combo ipilimumab + nivolumab confers a 46% intracranial response rate in patients with asymptomatic brain mets from melanoma.
The Study: In the phase 2 CheckMate-204, patients with at least one untreated brain metastasis < 3 cm were treated with ipi + nivo x 4 cycles followed by maintenance nivo without radiation with a primary endpoint of intracranial progression at 6 months. Patients had to be asymptomatic with no steroid requirement at enrollment. Over half of patients had unknown or <1% PD-L1 expression, and over half had a single brain metastasis. At 6 months, nearly 60% had a "clinical benefit" meaning either stable disease (2%), partial response (30%), or complete response (26%). Importantly, these rates were similar to the extracranial response rates—meaning the overall response to immunotherapy may be similar inside and outside the blood-brain barrier. What’s more, patients with higher (>5%) PD-L1 expression had double the rate of response (48 → 76%). We gave the Aussie trial a hard time, but these response rates aren’t too shabby considering these patients are typically getting immunotherapy anyway. Not to mention staging brain MRI will probably become more common for advanced and metastatic melanoma in the era of targeted agents. Plus, giving immunotherapy a chance to work in asymptomatic patients followed with serial imaging is reasonable keeping in mind that about half will respond. What we’re now left wondering: how should we treat asymptomatic brain mets from BRAF-mutated melanoma?
Bottom Line: Immunotherapy appears as effective inside the brain as outside and may not be a bad initial approach in patients with small-volume, asymptomatic brain mets from melanoma. Tawbi, N Engl J Med 2018


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