Anti-PD1 products FDA approved as first line treatment for melanoma

We have long known that response rates of 40% to anti-PD1 (Pembrolizumab/Keytruda  and Nivolumab/Opdivo) are much higher than the 15% response rates attained by Ipilimumab/Yervoy with much fewer side effects caused by anti-PD1 as well.  Even so, both anti-PD1 products (Pembro in September of 2014 and Nivo that December), were FDA approved as second line treatments for melanoma patients....meaning:  patients could only be given the drugs after they had failed to respond to ipi as well as BRAFi, if they were BRAF positive.  In October of 2015, the Nivo/ipi combo was FDA approved (with its much higher response rate of 50+%, and increased side effect profile to match).  In November, Nivo/Opdivo was finally approved as first line for advanced melanoma patients, albeit with a few caveats: Nivo/Opdivo approved as first line for melanoma

Just this month, Pembro/Keytruda has been approved for the same:
FDA approves Keytruda for first line treatment of metastatic melanoma
As best as I can determine, BRAF status is not a defining requirement, though "advanced" melanoma is, but it may be used in "untreated" patients.

But, as always seems to be the case with melanoma, there is a catch.  So far, the only treatment (other than inteferon) FDA approved as adjuvant (meaning available for Stage 3 or 4 patients who have no current, measurable disease...having had their lesions zapped with radiation or removed surgically) is ipi/Yervoy.  Ipi approved as adjuvant treatment for melanoma patients

However, all the additional FDA approvals do give me hope for NED patients.  Now that these drugs are FDA approved in their varied capacities, physicians have greater freedom to prescribe them as they see fit.  Hopefully, insurance payers will see the wisdom of providing coverage for more effective meds with fewer side effects over those with less efficacy and greater side effects (read costs)- even if they only look at it with an eye to their bottom line!  I will look at it as a way to ameliorate human suffering and combat a vicious disease. - c

Sew Chaotically! - McCall's M6842 - Skirt for Rosie

This skirt was easy and fun to make.  Attaching the flared circle skirt to the straight, 90 degree corners of the T-piece was a little different, though actually very similar to the way the Morris Blazer attaches the "collar".  But, I think it came together well and was a good way to use scraps from other garments (albeit ones yet to be made)!

Rosie really liked it and has already worn it in many different iterations!  I will probably be making another for her as well as one for myself!!!  Sew chaotically! - c

Artie...a beautiful soul, an amazing knight. Merde!

In the longitudinal study that followed 1 million British women over 10 years, recently published in the Lancet, despite looking at smoking, drinking, diseases, hormone replacement....the main outcome found was this:  Being stressed and grumpy and generally miserable does not shorten your life just as being happy and sweet fails to extend it!

npr.org: Study finds happiness doesn't guarantee longer life

The researchers were not surprised by this finding.  Much prior research has proven this notion already. The popular adage, "My PMA (positive mental attitude) is going to save me" not withstanding!  And don't get me wrong....I like positivity.  Hell, it gets me through a lot of days....if only because it keeps other people from strangling me!

But, as I noted here:  Oh, the people you'll meet

David Rakoff, the incredibly funny, journalist and writer (1964-2012), who experienced 18 months of chemo and radiation at the age of 22 when diagnosed with Hodgkin's disease, only to have a tumor that eventually took his life recur in his shoulder and metastasize, said it best in an interview with John Stewart:  "There was a study that showed that the long term mortality of people with lousy attitudes is no different from people with great attitudes.  So, you can be the worst bastard on the ward and you will not die at any greater rate than the other people.  People will simply be gladder when you do!"

Meanwhile, my heart is broken once again at the loss of one of the planet's sweetest, dearest souls.  Artie Vangampler lost his life to melanoma December 9, 2015 at the age of 48.   He experienced back pain in Nov/Dec of 2012.  Was told he had a pulled muscle.  By June of 2013 he was in a wheelchair with melanoma in his vertebrae.  Despite radiation, multiple bone mets developed rapidly. Zelboraf didn't help.  He completed ipi by Jan of 2014. Progression and incredible pain continued.  Additional radiation and Taf/MEK staved off his being paralyzed. By April of 2014, things had at least stabilized, he was able to walk again.  He started Keytruda that May.  By December he was dealing with choking, pressure and pain...again losing the ability to walk and thus losing access to many trials and treatments.  More radiation.  By April of 2015 he was doing some better, but scans showed more growth and tumors on his kidney. He switched from Keytruda to Opdivo.  He sought trial participation in Chicago, NIH and MD Anderson...but was turned down. July brought more radiation.  In October of this year, his local doc switched back to Keytruda, but added Abraxane.  And all of that is not even the important stuff.

Artie, arthurjedi007, to those of us who loved him on MPIP....was amazing.  He endured more pain and treatments and radiation (a misery all its own) than almost all of us.  He joined the forum as a really bright, but unassuming computer programmer who knew nothing about his own disease or the treatment options.  He quickly became a knowledgeable, kind, and generous expert.  No matter what he was dealing with personally....he was ever present with a kind word, a gentle, accurate suggestion and his trade-mark "I dunno..."  But...he did know.  He knew how to be there for people.  How to give of himself.

No...being the kindest, most positive guy on the ward did not save him.  But, he did save us.  I hope he knew that.

For a knight whose bravery and courage shown ever so much brighter than any Jedi, British agent or one of the round table. I am honored to have lived in your presence.  You made your mark my friend.  I will miss you.  But, I wish you peace.  - c

Ketchup!! (or....YAY!)

Thought it might be time for a little catch up....

• Got to visit with all my critters for Thanksgiving....each of them rooting for the other in the best way families do!
• My yard is swept of leaves, appropriate shrubs pruned, and hoses drained/stored for the winter.
• On a warmish day recently, all the windows got cleaned...weird timing perhaps...but I look OUT my windows far more during the winter than any other time!!
•  My house plants have been pruned and prepped and winter readied.
• All Christmas gifting is prepared!!!  Just a bit of wrapping and I'll be set!
• Some chaotically sewn (sort-of) tadah's are complete....no pics 'til January, though.
• Two flat tires on a cold, foggy, rainy, butt crack of dawn, drive to work...have turned into 4 new tires...after three trips to the shop and a fair quantity of $$$$$.  Thanks, Bentie!
• I am still getting in my elliptical workout or a run at least 4 times a week.
• Have had only one episode of wheeze so far this winter season and it was pretty easily tamped down with my albuterol/budesonide/atrovent hooka!  About par for my usual and certainly far less than when I was on Nivo/Opdivo.
• I had my eyes checked today, and while presbyopia has progressed a bit, no other problems, cataracts, bits or bobs or melanoma were discovered!
• My beautiful cherry trees survived pruning by the electric board with relatively little damage. 
• And then there's this...Washington Post: Jimmy Carter tells Sunday school class that he has no signs of cancer Jimmy Carter announces that he is cancer free after SRS to melanoma brain mets and surgery to a liver mass, (rendering him NED, I suppose) and starting Keytruda in August!  (Though Keytruda is not FDA approved as first line nor as adjuvant for most normal folks...but I'm still hoping that very soon the rest of us will be deemed worthy!!!!)

So.....  YAY!!! - c

PCR testing for circulating melanoma DNA....one mo one!!

Applications for quantitative measurement of BRAF V600 mutant cell-free tumor DNA in the plasma of patients with metastatic melanoma.  Schreuer, Meersseman, Herrewegan, et al.  Melanoma Res.  2015 Dec 3. 

"Small fragments of cell-free DNA that are shed by normal and tumor cells can be detected in the plasma of patients with advanced melanoma. Quantitative measurement of BRAF V600 mutant DNA within the cell-free DNA holds promise as a tumor-specific biomarker for diagnosis and therapeutic monitoring in patients with BRAF V600 mutant melanoma. Allele-specific quantitative PCR analysis for BRAF V600 E/E2/D/K/R/M mutations on DNA extracted from 1 ml of plasma is currently under evaluation in a number of ongoing prospective clinical studies. We report five patient cases that indicate the potential applications and utility of quantitative measurements of BRAF V600 mutant cell-free tumor DNA as a diagnostic test and as a therapeutic monitoring tool in stage IV melanoma patients treated with BRAF-targeted therapy or immunotherapy. Finally, we offer novel insights into the dynamics of cell-free tumor DNA in melanoma."

So this is the bandwagon many melanoma specialists are on at the moment as is evident by this article and the two recent posts noted below - all from differing sets of researchers! And, that's not a bad thing.  My cynical self sees it as a race to the patented, FDA approved, money making test...for this bio-firm or for that set of researchers.   My more hopeful self sees a potential method for minimally invasive, accurate diagnosis of the presence and type of melanoma an individual is dealing with, as well as a way to measure tumor burden and response to therapy.

Here's hoping!  - c

Circulating Tumor Cells...how they may eventually impact melanoma diagnosis and response to therapy

Circulating Tumor Cells, DNA, and mRNA: Potential for Clinical Utility in Patients With Melanoma.

Xu, Dorsey, Amaravadi, et al.  Oncologist. 2015 Nov 27.

Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and messenger RNA (mRNA), collectively termed circulating tumor products (CTPs), represent areas of immense interest from scientists' and clinicians' perspectives. In melanoma, CTP analysis may have clinical utility in many areas, from screening and diagnosis to clinical decision-making aids, as surveillance biomarkers or sources of real-time genetic or molecular characterization. In addition, CTP analysis can be useful in the discovery of new biomarkers, patterns of treatment resistance, and mechanisms of metastasis development. Here, we compare and contrast CTCs, ctDNA, and mRNA, review the extent of translational evidence to date, and discuss how future studies involving both scientists and clinicians can help to further develop this tool for the benefit of melanoma patients.

This article doesn't exactly provide any new or particularly useful data.  However, it does make one hopeful that work in this area will continue to advance so that we can have simple, standardized and reliable tests to measure and diagnose tumor status.  What a boon it would be to be able to diagnosis and follow tumor load and type, in order to better understand current status in patients, as well as response to therapy, without scans and the radiation, dye exposure and red herrings inherent in them.  Mostly, it is a call for more studies like the one discussed here: PCR Testing for melanoma

Best - c

Tia Nancy...

 
"I think that....sometimes, it is the people who no one imagines anything of - who do the things that no one can imagine."  ~ The Imitation Game

I have known Nancy (as well as her sisters, in-laws, nephews and nieces) for some ten odd years now. She has become a more impressive woman with every passing day, inspiring beauty, love, knowledge and an appreciation of life in all of us around her.  To her nephews and nieces, she is Tia Nancy.  In summers, holidays and sometimes after school (year round for the younger ones!) they happily attend Tia Nancy's School.  What a school it is!!!  Reading, writing and arithmetic for sure.  But, there is also art and dance and sports and community service!  And if that is not enough to keep one woman busy....there is her art...that she shares so genuinely and beautifully with so many.  Here is a very small peek into her inspiring world:

Love in all seasons.

Smart and amazing kiddo's...made even brighter through Tia Nancy's school and care.

Beautiful sisters.

Community service and cleaning up the neighborhood starts early.

Keeping the yard pretty.

Hard at work!

A family with the most indomitable spirit.

Has the necessity of 'hope' ever been put any better?

I love both of these.

A realization we can all apply.

I am so blessed and honored to be the recipient of this beautiful piece.

Nancy, you are truly beautiful and a blessing to those around you, having made the world a brighter, more hopeful place for so many.  Your support of me has been a gift more valued than I will ever be able to explain.  I love you. - c