Brain mets

work in progress

Background
Metastasis to the brain is one of the big challenges in Melanoma- cancer with the highest risk to spread to the brain  (43% in clinical studies and 75% in autopsies).


This session looked on therapies and how they worked on Melanoma brain mets:

COMBI-MB

Does Dabra/ Tram work in brain mets?

58% intracranial response, so response in brain mets
6.5 months time till progression, so less than extra-cranial

most common pattern progression: in the brain 47%

Results are now published in the Lancet here




CheckMate 204

Ipi/ Nivo in untreated brain mets

• 0.5- 3cm brain mets
• not symptomatic
• SRT on < 3 brain mets

good number of responses were already visible at 6 weeks


Conclusion

• Ipi/ Nivo works in the brain, but not quite as good as outside the brain.
• Need to find approaches sequencing with radiotherapy
• patients with brain mets need to be included into clinical trials

ABC trial- nivo vs ipi/nivo in active brain mets

Georgina Long

Interesting- small extra cohort of leptomeningeal disease

(pic)

Nivo and Nivo/Ipi have activity in brain mets

Activity is high when Ipi/Nivo is given up front


Conclusion

• Ipi/ Nivo high activity in brain mets when given upfront
• how to combine with radiotherapy

Discussion- Lynn Schuchter

This is about Melanoma patients with brain mets upfront who were often excluded from clinical trials.

Summary slide

Questions that remain
This data allows to consider upfront systemic therapy.

But which therapy first? How to sequence? How to combine with radiotherapy?

BUT
Ipi/ Nivo past Dab/Tram does not seem to work well for brain mets

Combination of Local therapy and Systemic therapy

principal take home messages

• systemic therapy as initial treatment has become an option

• honest discussion about prognosis important

Question from the audience-
anecdotal evidence: flare of brain mets after starting immune therapy? Occurs but not often.

Discussion point with G. Long

'Bulk control' for BRAF mut Melanoma- treat with targeted therapy for a short time to reduce tumour burden and then switch to immune therapy 'extremely attractive' as patients who switch to immune therapy AFTER progressing on targeted therapy do very poorly.




Abstracts


Abstract  9506  

COMBI-MB: A phase II study of combination dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600–mutant (mut) melanoma brain metastases (MBM).
Read full abstract here

Abstract  9508  

A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC).
Read full abstract here