CheckMate 204 Update: Practice-Changing for Brain Metastases?

Jeffrey S. Weber, MD, PhD


September 09, 2019

This transcript has been edited for clarity.

I am Jeffrey Weber, a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health in New York City.

An important abstract presented at the 2019 American Society of Clinical Oncology (ASCO) meeting reported an update of the CheckMate 204 study,[1] a phase 2 trial of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg induction therapy given to patients who had melanoma and previously untreated brain metastases. The initial CheckMate 204 study was published in 2018 in the New England Journal of Medicine.[2]

Patients in this phase 2 study predominantly had one to two brain metastases with a median tumor diameter of about 15 mm. Again, all of these metastases were previously untreated. This update included a cohort of 101 asymptomatic patients with a median follow-up of 20.6 months. The patients were relatively typical melanoma patients with an average age of 59 years. About 40% had LDH levels above the upper limit of normal. And they had a 50/50 spread of PD-L1 positivity and negativity; 78% had one to two metastases and 22% had three or more.

For this group of 101 patients with longer follow-up, the intracranial response rate has held at about 54%—very impressive. The extracranial response rate is 49%, which is as good as it gets for patients with only extracranial disease, meaning those who have no brain metastases. The clinical benefit rate, which adds the patients who were stable intracranially for 24 weeks or more, is 58%—again, an impressive number. The median time to response was 1.6 months. At 20 months' follow-up, 48 out of 55, or 87% of patients, had ongoing responses in the brain.

Looking at the progression-free survival inside and outside the brain, taking it all together, there's a nice plateau at about 24 months and the median progression-free survival has not been reached. At 12 months, overall survival is 82%, which is just about as good as it gets with only extracranial disease, and at 18 months, it's 75%. Again, that is quite impressive in patients who had one, two, three, or more asymptomatic melanoma brain metastases and were treated with ipilimumab plus nivolumab.

The estimated 6-month progression-free survival rate was 63%, and intracranial response rate was 54%. Median overall survival has not been reached with the median follow-up of 26 months. Regarding toxicity, no unusual or unexpected neurologic manifestations were reported.

This is practice-changing. The CheckMate 204 update reassures us that you can see long-term responders with metastatic melanoma in the central nervous system. This suggests that patients with asymptomatic brain metastases—especially those with low volume, small numbers of metastases—may not need stereotactic radiosurgery up front. It may be completely acceptable to treat these patients presumptively with ipilimumab plus nivolumab and then get an interim 6 week MRI scan, make sure they've not progressed in the brain, and continue treatment.

This is Dr Jeffrey Weber, talking about the CheckMate 204 abstract presented at the recent 2019 ASCO meeting. Please do send us your comments or questions. Thank you for your attention.

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