Melanoma treatment guidelines from Melanoma Big Dogs

As much as we've learned about melanoma, there remains much we do not know.  Yet, even with the limited available treatments, the stage and indications for use, what to do about side effects, what to do next, remains confusing for patients and oncologists alike.  To that end, I put together this primer a couple of years ago:  Melanoma Intel: A primer for current standard of care and treatment options  (Unfortunately, to date, it has required no up-dates other than the dosing schedule for nivo!)

There is also this post regarding adjuvant treatment, including data from a presentation made by Jeff Weber, MD (Melanoma Big Dog extraordinaire!): ADJUVANT therapy for melanoma!!!!!!!!!!!!!! State of the science....

And finally, also with the help of Weber's presentation, what may be coming in the way of immunotherapy and other treatments:  The future of immunotherapy and cancer - per Weber

 You can find more articles on most any particular treatment by entering the word in the search bubble to the top left if you are interested.  Now, as we head into ASCO 2020, Melanoma Big Dogs have put together guidelines for the use of systemic therapies in melanoma ~

Systemic Therapy for Melanoma: ASCO Guideline.  Seth, Messersmith ... Weber ... Agarwala, Ascierto ... Faries ... Sondak, et al.  J Clin Oncol. 2020 Mar 31.  To provide guidance to clinicians regarding the use of systemic therapy for melanoma, ASCO convened an Expert Panel and conducted a systematic review of the literature. A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma. In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma, while either of those two agents or the combination of dabrafenib and trametinib should be offered in BRAF-mutant disease. No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. In the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma, while those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF-mutant disease. Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines.

Click on the link included to search for specifics from the guidelines.  Hang tough peeps.  We're getting there! - c

For Kim!

Cancer sucks great big green stinky hairy wizard balls!  All day.  Every day.  It has no allegiance other than to destruction and chaos.  It recognizes no boundaries.  It strikes at will.  It is unfair.   At times it seems a burden that is too much to bear.  Yet love sees us through.

I am a huge believer in paying it forward.  However, today, as I honor my dear Kim who has been forced to join this crazy, painful, cancer journey, I hate so much that she should reap what she has so generously sown.  You see...

...this is my sweet Kim!!!!  Posing with my picture at our office because we had missed each other in real time that particular day!

Back in 2010, my incredible friends supported me and mine with more love and kindness than you can possibly imagine!!  Kim, furthermost to the right below, made the zillion ribbons you see worn in my honor at a "Beat the Beast" party before I was off to radiation and surgery for my brain and lung mets.

I have my ribbon still; precious among my talismans of love and strength with which I have been blessed.

In 2011, it was incredible to get to celebrate my return to work and hope as I joined my immunotherapy trial and got back into a more normal life.

Kim, Me, and Allison.  I am the blessed and lucky bug here!

And so today, I join the others who love her.  With appreciation for all she has given and shared with us.  Grateful for the love with which her generous spirit blesses all who know her.  She is strong.  She is wise.  She has an army of dear ones in her corner.  We are here, dear Kim.  We are here!  ~  Much love, c

Sew Chaotically! ~ A Dream Deferred - now realized!

Having learned the hard way that sometimes it really is best to eat dessert first, here's my finished room!!!!  I really love how it turned out!!!  Check out the story below...

Long ago, in the time before colon cancer (specifically ex-goblet cell adenocarcinoma of the appendix) and COVID, in other words August 2018, just before getting what were to be the last of my follow-up scans for Stage IV melanoma and leaving on an amazing trip to Italy, I decided to embark on a make-over for my "wooden couch" so dubbed by my dear one, Mary Ann!!!  HA!!! Brent and I bought this Pine Factory furniture when we first married and had the cushions re-covered when we moved into our current house.  So it sat.  Utilitarian.  Comfy.  But after twenty years of Karm and kiddos, definitely getting a bit worn around the edges.

No problem!  It was time for a change and I had imagined a vivid picture of what I wanted to turn it into!!! We found a shop to do the work.  A man who turned out to be a really cool and sweet guy came over to discuss reupholstering these pieces.  We picked out the fabric.  A few days later he picked up the furniture.  All was right with the world.  Well!  Moments later all hell broke loose!  My diagnosis, surgeries and colon cancer crazy soon followed.  He must have thought things were nutters indeed as B became very hard to get a hold of and the woman he had met who had been perfectly fine was suddenly hospitalized.  At any rate, thanks to his understanding and patience, eventually he and B worked out a time to trade furniture and payment.  I have not been able to thank him properly for the excellent work he did, til now!!!

During my convalescence, Ruthie helped me start the process!  We each did a piece of sashiko stitching on denim remnants while watching Big Little Lies.  An activity is always nice, isn't it, Shay??? For deets and close ups of Ruthie's excellent work and my sad results - check out this post - from November 2019 when I finally managed to turn them into pillow covers!  Sew Chaotically! ~ Sashiko pillow cases, done!!!  Yep!  For those who thought it couldn't be done - there is something that will definitely slow my ass down!  Chemo!  BLECH!!!! During that same period, I realized the throws and afghans were getting a bit ragged, too!  Well!  No worries.  I could certainly create a new one while sitting on my chemotherapied/CBD'd ass!  Indeed I did!  Sew Chaotically! ~ Crocheting under the influence....  Wonky though they were, with the first steps in the dream direction complete, there was a bit of rearranging to be done.  Captain chairs switched with rocker and recliner and - POOF!!!  Finally!  The perfect sitting area off the kitchen/dining room!!!

Speaking of POOF!!!  Since B's recliner has a foot rest and my rocker does not, I decided to make one!!!  Using scraps of denim and other leftover remnants within and without, I finished the POUF I'd imagined and been saving scraps for over the past several years just a few weeks ago! Sew Chaotically! ~ Stay home for you! Stay home for them! And, if you like, Make a POUF!!!

Following the pouf, I got busy on additional, long planned sashiko pillow covers.  The final step!!!  And when dear Kay gifted me some burgundy denim in just the right shade to match the wonky afghan and the pouf - BAM!!!  I got her done!

They are just simple envelope cases with overlapping pieces, that can open in the back, but close with cute buttons!!!  The sashiko pieces are appliqued on the front.  For all my prior sashiko embroidery I used regular embroidery needles.  For these bits I finally had a sashiko needle and while obviously not required, it has been a very nice improvement, as it is sharper and longer, especially considering the continued neuropathies in my fingers.

Somewhere along the way, I also crocheted the navy throw on the couch.  It, if I say so myself, is NOT woppy-jawed!  HA!!!  I should do one of those ads - a little compare and contrast of - "Your brain on drugs!"  - versus otherwise!!!  Still, with all the wonky and not so wonky pieces, I am very pleased with the results.  In this time of COVID, I offer this room as proof, that even when it seems least likely, a dream deferred doesn't mean forever.  Dreams deferred do not always "dry up like a raisin in the sun".  Sometimes, we just have to hang on.  Press forward, even if things are tilted on more than just their edges.  Together - we can reach our dreams - whatever they may be.  Thanks to each of you who helped me see this dream through. ~ love, les

#stayhome  #primarycolors  #hyggehome  #staystrong  #pulltogetherstayapart

The future of immunotherapy and cancer - per Weber

To finish my prior link, I'll share the remainder of Dr. Weber's report with you.  Check it out for yourself here -  Immunotherapy for cancer: the journey so far, and where are we headed? Cancer Crosslinks 2018 Jeffrey S Weber MD PhD

Advances in immunotherapy has benefited those experiencing a variety of cancers, not just melanoma:

Then there is the future.  Researchers are looking at ways to overcome resistance:

Work continues on successful vaccines that immunize against neo-antigens:

Efforts are being made to make adoptive cell therapy (ACT) with genetically modified T cells and tumor infiltrating lymphocytes more practical and economical:

New therapies and combinations are being developed:

The work to develop biomarkers that accurately predict outcomes continues:

So grateful to this man on a personal level with admiration for all of those who dedicate their lives to the care of and research for others.  It benefits us all.  - c

ADJUVANT therapy for melanoma!!!!!!!!!!!!!! State of the science....

Over the next bit, I am going to be digging into a presentation by Dr. Jeffrey Weber - see it for yourself here:  Immunotherapy for cancer: the journey so far, and where are we headed? Cancer Crosslinks 2018

With so many Stage III melanoma patients now gaining access to adjuvant care and all the inherent questions pertinent to that, combined with the fact that adjuvant treatment is what I attained for my melanoma journey, albeit as a Stage IV patient, I will start there.  Before we get into the weeds, here is an overview of current approved therapies for melanoma I wrote in 2017 that sadly, other than a change in dosing options for the administration of Opdivo, has not needed any significant updates since:  Melanoma Intel: A primer for current standard of care and treatment options
Here is an article that does pretty much the same thing, written in 2018:  Melanoma treatment in review

LATE ADDENDUM:  FINALLY!!!! There was reason to update the primer - April 2022 - Primer for Current Melanoma Treatments - New and Improved Version 2022!!!!

I recently penned some information for a Stage III patient dealing with the confusion that a melanoma diagnosis and adjuvant treatment can engender, and it seems a pretty good place to start:

It is very easy to get confused with all the "data" floating around.  Numbers repeated in the media (as opposed to medical literature) and unfortunately even occasionally tossed around in doctor's offices without clear explanation can create more confusion than clarity.  One of those oft quoted bits is the "50% survival rate" of melanoma patients vs various low rates from 10-20-something % that "melanoma patients used to have".  All of this can get confusing really quickly because you have to make sure you are talking about the right drug, used in folks in the stage you are discussing AND the right category of "response". Are the studies describing "response rate", "progression free response", "overall survival", or what?????? Those categories can mean very different things.  Further, I've seen lots of patients misunderstand the significance of the FDA approval dates for both targeted and immunotherapy as ADJUVANT vs the date of their approval for melanoma overall.  

Here's a little breakdown of FDA approval dates:

The first targeted therapy for BRAF positive melanoma patients was approved in 2011.  Targeted therapy for adjuvant use in melanoma was approved in 2018.

The first effective immunotherapy with its 15% response rate in Stage IV melanoma was ipilimumab (Yervoy - an anti-CTLA-4 product) ~ approved in 2011.  Its approval for use as adjuvant was in 2015.

Anti-PD-1 immunotherapy products, Nivolumab (Opdivo) and Pembrolizumab (Keytruda) were approved for unresectable/Stage IV melanoma in 2014.  Both have roughly a 40% response rate in those patients with a similar side effect profile that is less severe than that of ipi.  Opdivo was approved in combination with ipi for metastatic patients in 2015.  That combo is currently in trials as adjuvant.  Opdivo was approved for use as adjuvant in melanoma patients in 2017.  Keytruda was approved for adjuvant use in Stage III patients 2019.  {LATE NOTE:  Keytruda was also approved for Stage II patients in 2021.}

As a person who was likely somewhere between the 28th - 36th person in the United States to take nivolumab, via a clinical trial in the ADJUVANT arm as a Stage IV melanoma patient in 2010!!!!!!!!!!!! - I know from experience that it makes a HUGE difference in having a collection of data and information behind your treatment option and NOT!!!! Here's a little story that tells the history of Opdivo or as I took it - MDX-1106 - if you are interested:  Love Potion...or Patient...#9!!!!! 

The date of FDA approval for use in melanoma patients generally matters - even to those who are using it as adjuvant today.  In the case of Opdivo, it means that under FDA approval (apart from the fact that melanoma ratties in the United States had been taking Opdivo since 2009) melanoma patients were treated with Opdivo since 2014. Studies from us ratties as well as data that grew with the 2014 approval consistently show that folks with Stage III and Stage IV inoperable melanoma have response rates of around 40% when Opdivo is used as a single agent and through that use we learned what dosage to administer, the likely side effects, rare adverse events that might be encountered, how long they last, and how best to treat them. Important information that you do not have when a drug is first being used to treat a particular disease.

In all that trial and error - ie learning - researchers discovered that folks with melanoma responded best to immunotherapy when they had the least possible disease burden. This leads us to adjuvant therapy. Adjuvant therapy is given to a person when their tumor has been removed by surgery and/or radiation. Despite knowing since my trial - though the data wasn't published until 2014 - that we 33 ratties (2 stage IIIC and 31 Stage IV ) did very well when we took Opdivo as adjuvant, the FDA did not see fit to approve Opdivo for adjuvant use in melanoma until 2017. You can see the results of the adjuvant arm of my study here: C'est moi!!! Results from the 33 ratties in my Nivolumb/Opdivo trial...published! 

It notes: "Our data suggest that nivo is clinically active in resected stage IIIC/IV melanoma, based on low rate of relapse (10 of 33), impressive relapse-free survival - estimated RFS of 47.1 months, and median overall survival not yet reached with over 32 months of follow up." REMEMBER - we have learned even more since then!!!!!!!!!!!!!!!!!!!! 

Here is a report on ipi vs nivo in the adjuvant melanoma setting from 2017:  Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!!

That study shows ~ Recurrence free survival at 18 months: 66.4% for nivo 52.7% for ipi
OVERALL recurrence free survival was 70.5% for the nivo group (vs 60.8% for ipi) at 1 year...but...when you pull out the Stage IV folks the number was 63% for nivo vs only 57% for ipi.

NOW! When you break things down further, as the info above is beginning to show, folks who are Stage III do better than folks who are Stage IV no matter what you do or don't do to them. So you can't just take all the information gleaned from Stage IV patients and throw it at Stage III patients as fact. For instance, in the last report in this post from 2019, that addresses Stage III melanoma patients treated with Yervoy (which we already KNOW from the other report does NOT work as well for melanoma patients whether Stage III or Stage IV when used as a single agent compared to anti-PD-1) vs placebo noted in this link:  I've said it before, I'll say it again - ENOUGH ALREADY! No more interferon for melanoma!!! (Or placebos - for that matter!!!) You will see that Stage III melanoma patients, even treated only with ipi, had an "overall survival rate of 60% at 7 years". To be fair the placebo group had an OS of 51.3%. Hell, even I lived as a Stage IIIB melanoma patient for 7 years with no treatment beyond surgery before advancing to Stage IV and am still here after brain and lung mets and my nivo trial and remain NED for melanoma.

Bottom line - comparing apples to apples matters. The amount we have learned about anti-PD-1 since melanoma ratties started taking it in the States in 2009 and after it gained FDA approval for use in melanoma patients in 2014 makes a world of difference to all of us.

Now for the report from Dr. Weber, which begins with a review of immunotherapy for melanoma generally:

 Does immunotherapy work for patients with melanoma brain mets?  YES!!!

And with that history, we begin to explore immunotherapy as adjuvant for melanoma -

 This led to an intergroup trial testing 3 vs 10 mg/kg ipilimumab vs IFN-alpha -

Yep - this was me and my fellow ratties.  I was in Cohort 1.

This data justified a trial of adjuvant nivolizumab versus standard ipilimumab -

 NEXT - pilot nivo with ipi data justified a new adjuvant trial of nivo + ipi vs nivo with new biomarkers -

Forgive the blurry slides I've reproduced here.  Check the link at the top to view them for yourselves.  Hope this helps.  We've come a long way, though we have further to go.  Coming soon - the furture of immunotherapy for cancer....
Ratties rock! - c