Thursday, October 13, 2016

Stopping BRAF/MEKi after a complete response? Case study of 12 melanoma patients...


A question I know many BRAFi patients have....

Cessation of targeted therapy after a complete response in BRAF-mutant advanced melanoma: a case series.  Carlino, Vanella, Girgis, ... Ascierto.  Br J Cancer. 2016 Oct 6. 

It is unknown whether melanoma patients achieving complete response (CR) with targeted therapy can safely discontinue treatment.  All patients treated with BRAF/MEK inhibitors achieving CR and ceasing treatment before progression were identified. Clinical data at treatment initiation, cessation and progression were examined.  A total of 12 eligible patients were identified, with median follow-up of 16 months, of whom 6 (50%) recurred at a median of 6.6 months after treatment cessation. One patient lost to follow-up until presentation with symptomatic recurrence was the only relapser to die. At relapse, the remaining five patients had an LDH less than 1.2 times ULN, four were ECOG 0 and one ECOG 1. Baseline characteristics and time to CR and to discontinuation did not influence the rate of relapse. A large proportion of patients achieving CR with BRAF/MEK inhibitors relapse after treatment cessation. The optimal treatment duration in such patients is unclear, particularly where alternative treatments are available. 

Hmmm... Well that didn't work out so well for these 12 patients.  Perhaps...though small numbers with limited ability to extrapolate from....BRAFi patients with a complete response should switch quickly to immunotherapy before time runs out????? - Just thinking out loud.  My best to you all. - c

6 comments:

  1. I just published an article today (Brown Seaweed and Melanoma:An integrative hypothesis, Journal of Applied Phycology) and thought you might be interested in reading it. It is Open Access, so anyone can access it through Google. Best wishes, Jane

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  2. Dear Jane,
    Comments like yours....ie selling yourself and your own interests....are usually deleted from my blog faster than you can say, "Harajuku Girls"! Especially when these comments are completely off-topic from the post they are attached to - as yours is here.

    I have actually addressed alternative melanoma treatments many times, from coffee, to curcumin, to parsley and dill, to snake venom and mushrooms; you can check out the latest iteration here: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2016/08/everything-cures-melanomaredux5.html

    I've even addressed the incidence of melanoma in Japan, here in 2014: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/09/all-things-brafilatest-articles.html Stating:

    BRAF V600 mutations and pathological features in Japanese melanoma patients.
    Yamazaki, Tanaka, Tsutsumida, et al. Melanoma Res. 2014 July 19.

    Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500-2000 cases per year compared with 132000 per year worldwide) and frequency and distribution of BRAF V600 mutations are unknown. Testing methods were defined. BRAF V600 mutations were found in 41.8% of tested tumours. Mutation rate = more than 60% in patients aged less than 60 years and more than 36% of patients with stage III/IV disease. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas. 64.7% of superficial spreading melanoma, 50% of lentigo maligna melanomas and 20% of nodular melanomas.

    I'd have to do a little research to be positive, but those percentages for BRAF positive peeps seem about equivalent to folks in the states and Europe. As far as BRAF status, perhaps the Japanese do better in avoiding the sun and other risk factors (known or unknown) that contribute to melanoma...or there are genetic factors we don't even know anything about...that are keeping their rates of melanoma lower than those for the rest of us.

    I've posted the story of the development of anti-PD1, as Nivolumab (Now called: Opdivo, one of two anti-PD1 drugs available to melanoma patients) was first developed by ONO Pharmaceutical in Japan: http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/06/love-potionor-patient9.html

    However, I looked at your article. First, problem: You made many of the arguments against crediting sea weed ingestion as a protection from melanoma (as may be extrapolated by be the relatively low incidence of melanoma in Japanese populations) yourself. Japanese culture is anti-tanning, anti-obesity and may well have protective genetics....rather than reaping benefits from sea weed ingestion. One other downer, I have eaten sea weed, via nori, kombu and in sushi long before it was cool and still developed melanoma. For whatever that is worth.

    So...if you can cure melanoma with fungi (there IS pretty good data regarding shitakes!) or sea weed....I'm all for it. Just gotta keep it real here...for all the ratties.

    Here's Gwen Stefani for your enjoyment: https://www.youtube.com/watch?v=qecNL1266ms

    yours, les

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  3. Thanks for drawing my attention to this paper! I just downloaded the pdf. I guess the answer to the question I haven't yet asked my oncologist ("When can I stop taking this stuff?") is: Not until there is a damn good reason.

    I've been lucky enough not to experience any of the more common side effects of BRAF/MEKi therapy... but I have repeatedly had the least common one (eye troubles). Since that one has so far been manageable with steroid eye drops, I guess I am resigned to popping these pills indefinitely. Grateful to report I am now 18 months past brain mets and more than 2 yrs past lung mets!

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  4. Hey Deborah,
    So glad that you and many others are leading the way in long term stability on BRAFi. I guess the advice the research here is if you decide to stop your current treatment - switch to immunotherapy - quick! Wishing you my best! C

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