CheckMate 204: 'Practice-Changing' for Metastatic Melanoma

This transcript has been edited for clarity.

Hello. I am Dr Jeffrey Weber. I'm deputy director of and a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health in New York City. Today I will be discussing a very interesting study that was recently reported in the New England Journal of Medicine.^[1]

CheckMate 204 combined the immunologic drugs ipilimumab and nivolumab, the CTLA4 and PD-1 blocking antibodies, for treatment of patients with metastatic melanoma with brain metastases at first presentation. We have discussed preliminary data from this study, CheckMate 204, which were presented at the 2017 ASCO meeting, but now we have this more definitive report.

I believe this very interesting trial will be practice-changing. The report described 94 patients with a relatively typical distribution; median age was 59 years, two thirds were men, one third were women, with relative LDH levels above normal of about 40%, which is fairly typical for most metastatic melanoma trials. This was a phase 2 trial. About 40% of the patients had more than 1% PD-L1 staining, and about 36% had less than 1%. Some of the patients had previously undergone stereotactic radiosurgery. Participants were required to have at least one measurable lesion that had not been treated, but 90% of the patients had not been previously treated with radiation or stereotactic radiosurgery. Participants could have any number of metastases, but total size could not be more than 2 cm. Patients could not be steroid dependent or have significant cerebral edema, which frankly encompasses most patients with melanoma and brain mets at initial presentation.

The global response rate—that is, the response rate both intra- and extracranially—was an impressive 48%, which is similar to the response rate with ipilimumab and nivolumab at the standard doses given to patients who have no brain metastases. The response rate by classic criteria within the brain was 52% and was 47% outside the brain. These are very impressive data, with a 26% complete response rate in the brain which, again, is almost unheard of in any trial of patients with brain mets.

When you look at the swimmer plot of duration of response, 90% of the patients with follow-up of about 9 months on average have remained in remission globally, obviously including intracranially, so again that's very impressive. As one might imagine, in progression-free survival (PFS), the patients don't do quite as well as patients with no brain metastases in previous trials. Nonetheless, the PFS rate at 12 months was more than 50%, which is impressive. If you go back 10 years, overall survival was 4-6 months and PFS rate was about 2 months for patients with brain mets.^[2] So this is a very significant advance.

Finally, if you look at the overall survival data, they are not quite as impressive as in the CheckMate 067 trial,^[3] where 1-year survival was way over 80%. In CheckMate 204, 1-year survival overall was about 81% in patients with brain metastases, where a significant proportion of the patients had more than one metastasis. If you look at the overall study population, almost half of the patients had more than one metastasis, so this was not a trivial burden of tumor in the CNS.

This was a modest-size, 94-patient phase 2 trial. But with its publication in the New England Journal, I believe that it is a practice-changing study, because now patients may be able to forego stereotactic radiosurgery at the get-go and be treated with ipilimumab and nivolumab, with a reasonable chance of tumor regression and thus not needing to have radiation.

One caveat: When I treat patients who have brain metastases with this regimen, they can't be steroid-dependent and can't have significant cerebral edema or CNS symptoms, which still comprises the vast majority of patients. And I would get an interim 6-week MRI of the brain to make sure those tumors are regressing and certainly not growing. Nonetheless, very impressive data.

Please contact us if you have questions or comments. Again, this is Dr Jeffrey Weber. Thank you for your attention.

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