Thursday, January 7, 2016

BRAFi after BRAF inhibitors...Can you still gain a response?

In this post, see the second article noted:  BRAFi, What predicts resistance?
Researcher, Tolk et al., report that in those patients who recurred after initial remission in response to BRAFi, upon retreatment with BRAFi those patients experienced a 50% chance of regaining remission.  Along the same lines....another group of researchers offer this:

BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.  Roux, Pages, Malouf, et al.  Melanoma Rex.  2015 Sep 22.

"In around 50% of melanomas, the BRAF V600 mutation, resulting in activation of the MAP kinase pathway, is detected.  BRAF inhibitors have shown remarkable activity on the disease.  However, efficacy is short-lived in most cases, with a median disease-free survival of 6 months.  This short duration of response could be explained by the acquisition of resistance mechanisms.  Some cancers show sensitivity to the reintroduction of previously active drugs after disease progression.  We carried out a retrospective monocentric study on patients with BRAF V600-mutated melanoma who were re-challenged with BRAFi that were previously beneficial, but in whom the disease had progressed.  9 patients were included.  5 patients showed a subsequent partial response, 2 showed a dissociated response leading to clinical improvement, and 2 showed no radiological nor clinical response.  8 patients who had received re-challenge BRAFi had received an intercurrent treatment with ipilimumab.  These cases suggest that intermittent treatment with BRAFi could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials."

Well, not too much beneficial info here....other than the fact that in these 9 patients....7 did gain at least some response from their BRAFi re-challenge.  The implication of response after treatment with ipi is not made clear since we are not told which patients did what (though that info may be present in the complete article).  This post from 2014 offers several articles:  Data on BRAFi combos and effects of ipi before and after  , where in the last study, the only conclusion I could draw was this:  
"... for all their numbers, there was apparently no statistical difference in response whether you took BRAFi followed by ipi or vice versa."

Still with much to learn it seems!!!  Hang in there, ratties! - c

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