Sunday, 4 June 2017

Surviving Melanoma- overal survival data

work in progress


Melanoma therapies have evolved enormously over the last very few years. From only 12% patients surviving the first year after diagnosis- Alexander Menzies just called this 'the dark ages'- we are now looking at the possibility of true survival. What is still unclear is in which order therapies should be used, so looking how these medicines are working long-term is important.

Alexander Menzies- the BIG questions to ask:

- do we have true long-term survival- cure...? 
- who are the survivors?
- can we stop treatment?

Not long ago, 2-year OS would have been considered 'long-term survival'- not anymore.

This session gave updates from two different therapeutic classes: 
Immune therapy (Pembro) and 
Targeted therapy (Dabra + Tram).

Immune therapy

Caroline Robert on KEYNOTE-006
update results and outcomes of patients who stopped treatment with Pembro


interesting to note

  • Some (but few) patients get a complete response AFTER stopping treatment
  • 91% of patients who completed 2 years of Pembro are progression-free after a medium follow up of 9.7 months

Targeted therapy

Jeff Weber (instead of G. Long)

LDH level and number of organ sites associated with overall survival 

Comment on trial design
treated brain mets could be included but stable for 3 months
by consequence, not many brain met patients in the trial (pic)

Cross-over allowed (but we know that adding MEK to BRAFi at resistance is too late- Ribas at previous ASCOs), so lame

Combination better than monotherapy- 76 vs 54% but also, lower the dose of Trametinib reduces to 50% (check data, add pic)

interesting to note

  • NOT all patients receiving targeted therapy will progress
  • normal LDH level = better prognosis
  • <3 sites of metastatic disease = better prognosis

5 year overall survival all patients together: 28% 
but 5 year overall survival with patients with normal LDH and < sites of disease: 51%

13% PFS at 5 years on D/T- impressive- but only 4% patients are still on therapy


Alexander Menzies' summary

On survival vs cure

  • 50% OS at 3 years with Pembro and a plateau seems to be forming, similar to Ipi

  • 31% patients remain progression-free at 32 months 
  • but primary vs acquired resistance also exists for PD1

Can we stop treatment upon response?
Complete responders do better than partial responders or stable disease

Can we recover? So if we stop treatment, does the tumour respond again when we give the drug again upon progression.

Seems to work with MAPK but is less clear with PD1 less- not because it's not happening but because the data is not collected.

Is there something particular about the responders?
Seems so but we have to find out what it is.

General comment

'overall survival in the modern era'  with a number of effective therapies available, any OS data is affected by subsequent therapies, so therefore
PFS better endpoint to evaluate TRUE benefit


Abstract  9504  
Long-term outcomes in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in the phase 3 KEYNOTE-006 study who completed pembrolizumab (pembro) treatment. 
Full abstract here 

Abstract  9505  
Five-year overall survival (OS) update from a phase II, open-label trial of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600–mutant unresectable or metastatic melanoma (MM).
Full abstract here

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