Monday, May 8, 2017

Efficacy of Pembro (Keytruda) in melanoma brain mets

I posted this report in March:   SRS with any systemic therapy helps response in melanoma...but anti-PD-1 WITH SRS = best OS in brain mets

While the data has made it clear that brain mets resolve best when treated with SRS and immunotherapy (anti-PD-1 in particular), [Check out this post: Brain mets in melanoma: Don't wait to add anti-PD1 to SRS!!! And....TILs correlates with extent of brain edema and survival time in patients with brain mets ] there have been many actual, as well as anecdotal, reports of patients who had untreated brain mets...which then resolved while on anti-PD-1 alone.  I happen to be one such patient (though I had already had a different brain met radiated) and here's a report addressing others, with additional links to more articles at the bottom of the post:  ASCO 2016 - Immunotherapy in melanoma brain mets  
One of the links directs you to this:  Nivo (Opdivo) with radiation = better for melanoma patients with brain mets  
And there is also this:  Yep! Immunotherapy can work in the brain...and pseudoprogression can be real!!

Now there is this:

Retrospective Analysis of the Efficacy of Pembrolizumab in Melanoma Patients With Brain Metastasis. Dagogo-Jack, Lanfanchi, Gainor, et al. J Immunother. 2017 Feb 17.

A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab. Twenty-six (72%) patients with BM had received prior treatment for BM. With median follow-up of 17.2 months, 54 patients (61%) developed progressive disease on pembrolizumab. Intracranial progression occurred in 19 patients (21%), 3 of whom did not have BM before treatment. Median time to progression at any site was 6 months for those without BM (n=53), 5 months for those with treated BM (n=26), and 1.2 months for patients with untreated BM (n=10). Using a Cox regression model adjusted for baseline factors, there was a statistically significant reduction in the hazard of progression for patients without BM and patients with treated BM compared with those with untreated BM. In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM.

Basically, this report simply confirms all of the above.  Anti-PD-1 (pembro/Keytruda or nivo/Opdivo) work in the brain.  They work better when combined with radiation.  

There!  I said it....AGAIN!!! - c

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