Thursday, March 26, 2020

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

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 2019.
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

Monday, March 23, 2020

Sew Chaotically! ~ Stay home for you! Stay home for them! And, if you like, Make a POUF!!!

Though young healthy folks are less likely to develop more significant illness, it has become abundantly clear that no human is immune to COVID-19.  As such, staying home and adopting social distancing when being out in public is required, provides the best way for us to protect our own health and the health of those most at risk among us.  Still, those who are providing essential services or without 'work from home' options must carry on.  These facts make this plea from healthcare workers who are putting their lives on the line to care for all of us even more important:

With all that is going on in our world and the inherent worry involved, I am fortunate to be able to stay home without much difficulty, but I've found it hard to sit down to my machines for garment making.  I'm sure I'll get back to it, but in these recent unsettling days I've spent a lot of time in my garden, running, reading, listening to way too much COVID-19 analysis on TV, and doing some pretty awesome workouts via MADFIT.  Who knows?  I may come out of this with rock hard abs!!!  Brent and I have dedicated some time to study "homemade mask making".  We've settled on fabric and a pattern that we think will make them most useful.  He even ordered some medical grade fabric that we will use as inserts - if it arrives.  I will be giving more updates on that as we get along.  I did enjoy hand stitching new binding on these oven mits whose edges had become much frayed.
I think they turned out pretty cute!  At the very least their useful life was certainly extended!
I used self made binding with my last bit of this fabric from Frou-Frou Paris originally made up in this Archer, pattern from Grainline Studio.
That success - both in creating something I deemed useful and in distracting while simultaneously focusing my attention - I then embarked on completing a POUF - a project I've been working toward for sometime.

B's recliner has a foot rest he can put up or down.  My chair does not.  Never fear - a pouf to the rescue!  I looked at purchasing one, but they weren't quite what I wanted.  Then I discovered the FREE POUF PATTERN and tutorial by Closet Case Patterns!!!  I could do that!!!  Gradually, I put together fabrics (scraps from various makes) that I thought looked nice together and in my living room.  After collecting random bits for some time, this is what I came up with -

For the longest, I have kept this basket beneath my machines.  I toss all little bits clipped off seams, strips left after serging, along with other fabric remnants too small for use as other garments, bindings, pockets, or quilt squares.
As the basket filled, I stored these bits and pieces.  Over time it really piled up!!
Putting the POUF together was easier than I feared!  The only tiresome part was interfacing all my pieces.  While not required, I did it so that, hopefully, my pouf will be around for a long time!  The pattern includes instructions for placing piping around the circle's edges, but not having any nor the items needed to make it, I just rolled without it.

I think she turned out pretty cute!
Because of the height of my chair and how I wanted to rest my legs, I did make my pouf about 3 inches taller than the Closet Case version.  Making things the way we want them is why we are makers, right????  I placed my scraps in two flexible tall kitchen garbage bags within the pouf and that worked well.  (There is a zip on the bottom.)  That way, I'll be able to remove the stuffing fairly easily and wash the covering should I ever need to.   Be warned!  This girl is heavy and holds a lot of stuffing!  But, I already love her!!!

SEW!  Stay home.  Be safe.  Do what makes life better for you!  Maybe even make a POUF!!! - love, les

Friday, March 20, 2020

And it was all yellow...

Yellow ~ by Coldplay

"Look at the stars.  Look how they shine for you.  And everything you do.  Yeah they were all yellow...  It's true.  Look how they shine for you.  Look how they shine for you.  Look how they shine for you..."

Did you know you can "force" forsythia blooms indoors?  Yes, you can!!!  Just clip some branches in early spring, place inside in a glass of water - and there you go - BEAUTY!  Even better, when you're done with them, stick them in potting soil outdoors and you have a new plant to enjoy for years to come!
Beauty remains.  It is still there, even if these are times that make us look a bit harder to find it.  Thanks, Coldplay.  From my yard to yours ~  "Look how they shine, look how they shine for you.  ~ And it was all yellow."   Love, les

Thursday, March 19, 2020

LIVING ironically ~ post cancer and during COVID-19 ~ Welcome to the world, baby girl?????

Isn't it ironic???!!  Having been in personal isolation for the past year and a half due to my surgeries in 2018 for adenocarcinoma ex-goblet cell of the appendix and subsequent chemotherapy - I was very much looking forward to rejoining the world this spring!!!  I had fun working on Roo's spring wardrobe.  I cleaned ALL my closets and cupboards.  Scrubbed the baseboards, refrigerator, every tray and drawer in the kitchen.  Oiled and cleaned under, beside and behind the furniture.   Spring cleaning done early!!!  I was ret tah go!  Enter COVID-19 necessitated social isolation!!!

To explain ~ My second episode of malignant cancer and its treatment proved incredibly difficult to rebound from - physically and mentally.  Not news to any cancer patient, but old school chemotherapy is a bitch!  I continue to live with significant neuropathies especially to hands and feet (a burning pain mixed with strange numbness and weird jingy jangy sensations) along with a variety of skin afflictions and joint pain that are improving.  Sadly, these side effects are incredibly common with chemo.  Every patient forum for cancer treated in this manner, has a zillion posts from folks dealing with similar side effects, all searching for help and answers.  Too often, oncologists provide no particularly valuable warnings of what is coming nor advice on how to deal with these issues once present.  Even worse, there is often an undertone of, "You had cancer.  You're still here.  Are you not grateful?"  You may be sent to rheumatologists or dermatologists. (I declined.) Still - no real solutions are provided.  X-rays and scans of joints are usually negative. Patients are often told that "nothing is wrong".  Skin weirdnesses are very common.  Soon after starting chemo I developed thick waxy yellow plaques to my face, arms and hands, improving some once off chemo.  Since then my skin in those areas has peeled repeatedly.  My joints - and bones generally - hurt everywhere, all the time, during chemo.  With chemo completed, the generalized pain improved, but my joints continued to ache.  What's a girl to do?  I started short workouts on the elliptical.  I took walks.  I began to run.  It hurt.  But, today the joint pain is better.  I started using some OTC retinol products to the plaques on my hands and face, based on some research B found.  They improved gradually.  Apropos of nothing, my face will still randomly peel, but the plaques have resolved.  Neuropathies remain pretty much unchanged, waking me some nights, not on others.  It is what it is.

Mentally, it has been a struggle.  It was hard to accept the need for help from others.  Hard to be the cause of worry - again!  Hard to lose the "future" I had drafted for myself.  Hard to make garments - something I had been excited about - for a body so radically changed.  A body that may not need said garments period.  Besides, a body not going out and about can't justify the production of new clothing, can it?  Self worth is hard to find when you don't seem to be doing anything productive!  But gradually, through the love and encouragement of my dear ones, the beauty of books and nature, the resilience of the human spirit - I began to MARCH FORTH!

Over the past few months, I have taken baby steps to rejoin my world.  Roo's wedding.  Visiting friends engaged in their own struggles.  Sewing projects for myself and others.  A bit of travel with B.  Finally feeling free to play!  I even got a job!!!  YEP! Sho did!  As a Census Worker, to begin later this summer, a useful and interesting way to start being a productive human once again.

Which brings me back to IRONY and COVID-19! Just as I attained the strength to end my personal sequester, our globe has been attacked by nasty strands of RNA using human cells to replicate and grow.  Like cancer, COVID-19 is not impressed with how much money you have, the color of your skin, the state or country in which you live.  Neither cancer nor viruses value maps.  They are not deterred by walls or lines drawn in the sand.  It is immaterial to them who you vote for - or against.  They don't care if you are young or old.  However, the data for this particular virus tells us that the older and immune-compromised among us are at greater risk for significant illness.  THIS DOES NOT MEAN THAT YOUNGER FOLKS WON'T GET INFECTED!!!!  It just means they are somewhat less likely to be at risk for hospitalization and death.  Given the numbers expected to be infected in the US (and across the globe) and the data already demonstrated regarding the proportion who will require hospital care - it is clear that if the outbreak is allowed to occur all at once, the capacity of our healthcare system to provide care to all who need it - both the suffers of COVID-19 and those with heart attacks, strokes, appendicitis, trauma and all the other expected illnesses those systems address daily - would be overwhelmed!  Therefore, it is obligatory for all of us to do our part to slow the spread of this virus as much as possible in order to ensure the availability of healthcare resources for those who need them.  Apart from needed testing, the common sense action we can all provide to stem the tide, is social distancing.  It is just that simple.

As disappointing, frightening and strange as this new reality is - WE CAN DO THIS!!!  Last Friday, Roo was told - starting Monday you will teach online - from home.  Okie dokie then.  A bit of brain storming with fellow teachers and she is up and running.  Work and assignments posted on line.  Videos of instruction produced at home.  Check her utube channel Moore Math with Mittens if you want to beef up your geometry and algebra 2 skillz!!!! I am so incredibly proud of her and teachers across the globe who are stepping up to meet the needs of their students on incredibly short notice with lots of love and creativity!!  Sadly, for many children in this country, their school lunch is the only significant meal they have.  At Roo's school her principals (already amazing multi-taskers and certified bus drivers) are traveling the bus route, taking lunches to students along with delivering and picking up printed school work to students without internet access while simultaneously working to get those kiddos online! She and ever so many other teachers have stepped up to this unprecedented challenge, keeping our nation learning and our kids busy and comforted by caring faces - even if they are only "virtual"!!

You parents are awesome, too!   Granted, it is more than you ever asked for, but I know you are are doing a great job for your kids and the rest of us really do appreciate you for it!!!  Still, responses to this new arrangement posted by some of my friends with kids at home have made me laugh out loud:

There are all the unsung heroes of our everyday now juggling even greater burdens - the delivery workers (from mail, to food, to products), checkout clerks, grocery employees of all stripes, pharmacy staff, all our healthcare personnel - from housekeeping to radiology to respiratory therapy to nurses to doctors and everyone in between ~ blessings, gratitude and strength to you all.

Then, there's this guy!  Petrified of bringing crud home to me - given the history shared above, having had asthma from childhood, donating half of my right lung to melanoma and wheezing my way through 2 1/2 years of immunotherapy in that ta dah - this is the crazy get-up that B donned to make a run to Wally World yesterday!  He didn't really think his attire was going be completely protective against the corona virus, but did report being the recipient of a lot of side eye and folks definitely gave the #crazperson a wide berth - which was exactly what he wanted.  That pic cracks me up every time I see it!!!

Yes, things feel out of control.  Plans made even days ago - from the mundane to the adventurous - are turned on their head.  Loved ones may suffer.  Elderly in nursing homes are most certainly confused with new routines and the absence of expected visitors.  Children are at loose ends.  Parents are burdened further.  The global economy and incomes of friends and family will certainly be affected.  Jerks - IN MY HOMETOWN!!!! - try to benefit from the desperation of others:  He has 17,700 bottles of hand sanitizer and no where to sell them  WHAT AN A$$HOLE!!!!!!!!!!  But, despite disease, difficulties and despicables - the world is filled with beauty still.  A young family in my neighborhood volunteered to make grocery runs for those who are unable to do so for themselves.  Brent and I are searching for ways to put our skills and training to use. Yes, personal dreams and plans have been for the moment dashed. But, if ever there was a time when society was blessed with the technology to allow physical distancing WITHOUT social isolation, it is now.  As we cancer survivors have already learned, when shit hits the fan, that which is most important in life comes to the surface very quickly and the rest - didn't really matter after all.

Stay safe.  Take care of yourself.  Take care of each other.  Alone we are little more than ripples in the sea of life.  But together, we can do great things.   Love, les