Tuesday, October 24, 2017

Melanoma Brain mets - things are getting better - SLOWLY. AND....Yes, you SHOULD COMBINE radiation and immunotherapy!!!!

You may recall I've mentioned this once or twice ~ Melanoma brain mets suck GREAT BIG GREEN HAIRY WIZARD BALLS!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!  And if that's not clear enough...there's this:

Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies. Sloot, Chen, Zhao, Weber, et al.  Cancer. 2017 Oct 12. 

The development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies.

Patients with unresectable AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified. Data were collected regarding patient characteristics, stage of disease, systemic therapies, MBM status/management, and overall survival (OS). The risk of de novo MBM was calculated using a generalized estimating equation model and survival comparisons were performed using Kaplan-Meier and Cox proportional analyses.

A total of 610 patients were included, 243 of whom were diagnosed with MBM (40%). Patients with MBM were younger, with a lower frequency of regional metastasis. No significant differences were noted with regard to sex, BRAF status, or therapeutic class. The risk of de novo MBM was found to be similar among patients treated with chemotherapy, biochemotherapy, BRAF-targeted therapy, ipilimumab, and anti-programmed cell death protein 1/programmed death-ligand 1 regimens. The median OS of patients with MBM was significantly shorter when determined from the time of first regional/distant metastasis but not when determined from the time of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5 months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from 2000 to 2008, 2009 to 2010, and 2011 to the time of last follow-up.

Brain metastases remain a common source of systemic treatment failure. The OS for patients with MBM has improved significantly. Further research into MBM prevention is needed. 

So....40% of the 610 patients in this study developed brain mets.  They tended to be younger with a "lower frequency of regional metastasis."  Sex and BRAF status made no difference.  Overall survival from brain met diagnosis in 2000-2008 was 7.5 months.  If diagnosed from 2009-2010 OS was 8.5 months.  If diagnosed with a brain met from 2011 to last follow-up was 22.7 months.  Yep. That still sucks...but it is certainly better and it is more than clear that radiation combined with immunotherapy is a big part of that improvement!

Oh wait!  That reminds me!  I've been yelling this repeatedly, too!!!!! - YES, YOU CAN COMBINE RADIATION WITH IMMUNOTHERAPY FOR BRAIN METS!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!  AND, when you do....patients do BETTER!!!!

Here's a recent post to that effect...and a link to a zillion more articles within:  Radiation and immunotherapy...not just safe together...but better!!! (AGAIN!!!)

Now, this:

Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. Anderosn, Postow, Wolchok, et al.  J Immunother Cancer. 2017 Oct 17.

Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy.

From an institutional database, we retrospectively identified patients with melanoma brain metastases treated with radiation therapy (RT) who received concurrent pembrolizumab. Concurrent treatment was defined as RT during pembrolizumab administration period and up to 4 months after most recent pembrolizumab treatment. Response was categorized by change in maximum diameter on first scheduled follow-up MRI. Lesion and patient specific outcomes including response, lesion control, brain control and overall survival were recorded and descriptively compared to contemporary treatments with RT and concurrent ipilimumab or RT without immunotherapy.

From January 2014 through December 2015, we identified 21 patients who received concurrent radiation therapy and pembrolizumab for brain metastases or resection cavities that had at least one scheduled follow-up MRI. Eleven underwent stereotactic radiosurgery (SRS), 7 received hypofractionated radiation and 3 had whole brain treatment (WBRT). All treatments were well tolerated with no observed Grade 4 or 5 toxicities; Grade 3 edema and confusion occurred in 1 patient treated with WBRT after prior SRS. For metastases treated with SRS, at first scheduled follow-up MRI (median 57 days post SRS), 70% (16/23) exhibited complete (CR, n = 8) or partial response (PR, n = 8). The intracranial response rates (CR/PR) for patients treated with SRS and concurrent ipilimumab and SRS without concurrent immunotherapy was 32% and 22%, respectively.

Concurrent pembrolizumab with brain RT appears safe in patients with metastatic melanoma, and SRS in particular is effective in markedly reducing the size of brain metastases at the time of first follow-up MRI. These results compare favorably to SRS in combination with ipilimumab and SRS without concurrent immunotherapy.

So here, 21 patients had CONCURRENT radiation to brain mets, or the area they were surgically removed from, while taking pembro.  Only one patient had brain edema and confusion, having been treated with WBR after prior SRS.   

After all that...yes, melanoma and melanoma brain mets are horrible.  No, we have not improved survival nearly enough.  BUT....we have made progress.  And to attain those improved results for yourself...be sure that your oncologist and radiologist fully understand that brain mets can (and should!!) be treated with concomitant radiation and immunotherapy.  If they do not understand that fact....RUN....to a physician who does.  You deserve every chance to have the best possible results if you are dealing with melanoma brain mets.  For now...combining radiation WITH immunotherapy is the best treatment we have.  Make sure YOU get it, if you are in need!! - c

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