Should Melanoma Brain Met patients be allowed in clinical trials???

It still hurts my heart (and my head) that so many people fail to see reason and understand why many of the new treatments for melanoma can't be viewed like old time chemo when it comes to deciding whether to allow melanoma brain met patients to have them!!!  When thinking about the use of novel therapies (ipi and anti-PD1) in regard to brain metastasis, studies and the method of action of these drugs make it clear that the action upon brain mets is NOT due to the DRUG "crossing the blood brain barrier," but for the activated cytotoxic T-cells to do so. In my own study of resected metastatic melanoma patients with Nivo, all 6 of us who had metastatic brain mets out of the 30 in our arm, begun in 2010, were still alive and kicking with NO RELAPSE as of September 2013. Weber and many other researchers have contended for some time that drugs like Ipi and anti-PD1 have as good an effect in the brain as they do in the body. Additionally, in a nivo treatment arm at Moffitt that allowed brain met patients, 1 of the patient's brain mets resolved on nivo ALONE...with NO OTHER TREATMENT. To say they are excited is a definite understatement!

In his presentation and interview @ ASCO, June 2013 - Melanoma: Long overall survival in patients receiving Nivolumab, ...When asked about the likelihood that the drug works on brain metastases, Sznol noted that this trial excluded patients with active brain lesions, but accepted patients with previously-treated central nervous system tumors. Therefore the answer to the question remains unknown. "But we have long-term responders who didn't develop any brain metastases, so that suggests that maybe we are controlling disease in the brain," he said.

Phase II trial of ipi monotherapy in melanoma patients with brain metastases, by Lawrence et al.
CONCLUSION: Ipi has a similar level of activity in brain and non-CNS lesions.

Novel treatments for Melanoma brain Metastases, by Kenchapp et al. 2013. Looked at a study using ipi..."this study revealed that ipi has activity in melanoma brain mets...it is unknown whether the treatment was more effective in larger melanoma brain mets in which the highly permeable blood brain barrier may allow greater ingress of activated cytotoxic T cells."

And finally, Melanoma Brain Metastases: Is it time to reassess the bias? By: Flanigan, Sznol, et al. July 2012. These authors note that melanoma brain met patients are typically excluded from trials. They conducted a chart review of 251 metastatic melanoma patients diagnosed after 2005 to evaluate them in the context of eligibility for treatment with novel agents. And "found median survival of malignant effusion (mets in the pleural cavity) patients was significantly shorter than brain met patients (2 vs 8 months)." Therefore, "exclusion of melanoma brain met patients from clinical research programs is no longer justified and alternate investigational approaches, possibly combining local and systemic therapies, are greatly needed for these individuals."

So....lots of folks ARE on our side!!! Hopefully, archaic, irrational decisions will give way to what the data shows very soon and more patients with metastatic melanoma mets to the brain will have greater treatment options, as the data shows more and more the reality of our situation. - c