Wednesday, June 8, 2016

ASCO 2016 - Immunotherapy in melanoma brain mets

Brain mets suck balls.  No other way to look at it.  Been there, done that.  But...there is hope....


Immunotherapy-treated melanoma brain metastases within the French national cohort, MelBase.  ASCO 2016. # 9556.  J Clin Oncol 34, 2016.  Allayous, Calle, Lacour, et al.

Background: Melanoma brain metastases (BM) are associated with poor prognosis. Although novel therapies such as ipilimumab (IPI) and anti-PD1 (aPD1: nivolumab and pembrolizumab) have shown their efficacy in BM, little information is available in their use in BM. We report the efficacy of immunotherapy treatment on melanoma BM in “real-life” condition within MelBase. Methods: MelBase is a French multicentric clinical and biological cohort dedicated to the prospective follow-up (FU) of adults with unresectable stage III or stage IV melanoma. Since March 2013, 754 patients were included (25 centers). Available data were collected (11/21/15) and analyzed (demography, overall survival (OS), progression-free survival (PFS), response rate). Results: 2 subgroups are presented: BM treated with IPI (sgI) and BM treated with aPD1 (sgaPD1).The characteristics at the initiation of the treatment are: SgI (n = 39): mean age was 61 years, 82% were PS 0-1, 32% had elevated LDH, 67% non-mutated BRAF. Median FU was 11.2 months. OS was 6.6 months (IC95 :4.7−12.5), PFS 2.4 months (IC95 :1.8−3.4). 29 patients were evaluated: 7% complete response (CR), 3% partial response (PR), 17% stable disease (SD) and 72% progressive disease (PD). The best overall response (BORR) was 8% and disease control rate (DCR) was 21%. In sgaPD1 (n = 39): mean age was 56 years, 79% were PS 0-1, 45% had elevated LDH, 49% non-mutated BRAF. Median FU was 5.6 months, OS 5.5 months (IC95 :3.7-not reached), PFS 2.8 months (IC95:2.4-not reached). 30 patients were evaluated: 3% CR, 13% PR, 18% SD and 44% PD. BORR was 15% and DCR 33%. Conclusions: IPI results are consistent with data published by Margolin (2014) and Queirelo (2015) with DCR ranging from 24 to 27% and median survival from 4.3 to 7.0 months. Concerning anti-PD1, our results are also consistent with DCR observed in Harriet (2015) study on 18 patients. We show the first survival data obtained in patients with BMs treated by anti-PD1. Although direct comparison is difficult outside a controlled study and aPD1 data need to mature, IPI and aPD1 show comparable efficacy in melanoma BM lower than efficacy with BRAF inhibitors.

...and this....

Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition.  Lüttmann, Grätz, Haase, et al.  Melanoma Res. 2016 May 30. 


Although 40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.

Use the search bubble to find much more....but there are these:
Nivo/opdivo with radiation better for brain mets
Yes Virginia, both immunotherapy and BRAFi work on melanoma brain mets
Yep! Immunotherapy can work in the brain!

Thanks, ratties!!!!   - c

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