Ooops! Opdivo (Nivolumab), did it again...this time it's approved for Liver Cancer

To back up a bit...here's some history, Opdivo style:

2014 - Opdivo (previously known as ONO4538, then MDX1106 [as it was called when I first started taking it], then BMS936558, then Nivolumab, and finally...Opdivo...dun, da, da dun!!!!) was approved for advanced melanoma patients after they had failed ipi and, if BRAF positive, BRAFi as well.
2015 - Opdivo was approved as a first line drug for unresectable or advanced melanoma, BUT....you had to be BRAF positive - though there was an abundance of data demonstrating that BRAF status made no difference!!!
2015 - also saw Opdivo approved for use in advanced renal cell carcinoma as well as non-squamous and non-small cell lung cancer, after platinum based chemo.
2016 - FINALLY,  Opdivo was approved for use alone or with ipi, in advanced melanoma patients, no matter BRAF status.

Now....

Bristol-Myers Squibb’s Opdivo® (nivolumab) Receives FDA Approval for the Treatment of Hepatocellular Carcinoma Patients Previously Treated with Sorafenib

That's all great news.  The more help provided to cancer peeps the better!!  NOW!!! How bout seeking approval for folks with Stage III melanoma, hmmmmmm???  I think we ratties have more than provided the needed data....with this research pretty much saying it all:  Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!! 

Check out the link...or....here it is in a nutshell:

Stage IIIB, C, or Stage IV melanoma patients were allowed...even those with brain mets...as long as all were completely resected.

Patients joined from March 2015 to November 2015

There was a 5% cutoff for PD-L-1 staining (ie positive for PD-L-1 staining on tumors)

Nivo was given at 3mg/kg every 2 weeks or ipi was given at 10/mg/kg every 3 weeks for 4 doses then every 12 weeks.  Either drug was given for one year.

Patients were assessed via CT's of body and MRI of the brain every 12 weeks for 2 years, then every 6 months until year 5.

905 patients were studied, none of whom were still getting the drug by the final report.

Only 397 of these patients completed the full year of drug treatment.

Of the 452 in the nivo arm, 275 completed the year.  Of the 453 in the ipi arm, 122 completed.

Nivo outcomes were better than ipi no matter the patient's age, sex, disease stage, or BRAF status.  Nivo had fewer side effects.

In prior studies, ipi has demonstrated a pretty consistent 60% recurrence free survival in Stage III NED patients when used as adjuvant.  That number held in this study even when Stage IV patients were included.

Recurrence free survival at 12 months:

70.5% for nivo                    60.8% for ipi

Recurrence free survival at 18 months:

66.4% for nivo                    52.7% for ipi

Median distant metastasis free survival was not reached in either group.  However, it was longer in the nivo group with mets developing in 93 of the 369 peeps in the nivo group and in 115 of the 366 ipi group.

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.

Call it by any name you like, BMS!  Let's get THIS approval DONE!!! - c

Travel Chaotically! - London and the Cotswolds!! (and fabric shopping!!!!)

I am such a lucky girl!!!  We just got back from a lovely visit to London and the Cotswolds.  The A##hole who decided to try to blow up part of the London tube:  London tube bombing: PM says terror threat level raised to critical  be damned!!!  (Along with the jerk who, almost a year ago to the day in September of last year, tried to create havoc in New York and New Jersey during our visit there:  Travel Chaotically! - New York - Street Fair and Central Park!)

Instead of giving any cred to such weirdo's, I'll tell you what is really important!!!  The real live wonderful people we met and shared our visit with ~ Dave, Clive, Ibrahim, Amal, Batsy, the proprietress of the Persian restaurant, the little boy there that we taught to fist bump, the couple with family in Turkey (and the US) in the fabric shop in Walthamstow, the lady who better be making her fleece jacket so she won't be cold when she's out with her walking club, the Welsh couple and the bar keep at The Black Bear Inn....and ever so many others!!  I have SO MANY STORIES!!!!  (Plus, I have yet to share the remainder of last year's New York trip, that took off from there and explored Paris, Sarlat, and Marseilles!!!)  B took a great many more and better pics than I did...but lest it be a whole year before I get around to it....I wanted to share these snippets of memory with you now....

Classic!  X's three!  As in: 1) The quintessential British phrase.  2) Big Ben.  3) B being the worst person in the world to take a photo of, as he is constantly looking at HIS camera!

Boat trip along the Thames!  The London Eye (big ferris wheel in the background) cannot be avoided!!!

Back side of the Tower of London.

A little cuppa and a 'pick-me-up' along the Thames.

A change from our last visit...about 10 years ago...are the bollards that now line many London streets.

Westminster Abbey

Train station, watching the board to learn the platform at which the train will appear, for our trip to the Cotswolds.

We stayed in Moreton-in-Marsh at the Bell Inn (supposedly the Inn and area that inspired Tolkien's tales of Hobbiton and Inn, The Prancing Pony) and visited Stow-on-the-Wold and Bourton-on-the-Water!  Loving these names!!!  If only we had also visited Wotton-under-Edge and Fuddlebrook!

Hiking along the public footpath!

My cutie!!!

Learning to Belly-up-to-the-Bar!!!  The Black Bear Inn!

Back in London.  Lovely visit to the British Museum and the National Gallery.  Emotive Turners.  Exquisite Dutch Masters.  Beautiful Monets.  Great chats with various floor watchers.  Such decadence.  And it's FREE y'all!!!!  I mean they ask for a donation...but seriously!!!!  You do have to pay to pee in the city, though.  It'll cost you a pound in London, but only "20 p" (Yes, it is actually said like that - Twenty P [pence]!!!) in the Cotswolds at the "Public Conveniences".  But, you can pee for free in pubs, restaurants, museums and galleries.  The more you know....
Oh.  And, yes.  That is a thumb in the pic above.  No.  I cannot explain the phallic nature of it!

My silly B before seeing "The Mousetrap" in London!

One of his many "Full English" breakfasts!

Fabric shopping in Walthamstow AFTER checking out all the shops around Oxford Circus along Berwick Street AND Goldhawk Road at Shepherds Bush Market!!!  I loved it all, but REALLY, REALLY enjoyed Walthamstow Market along High Street.  SO. ABSOLUTELY.  FABULOUS!!!!  Great thanks to Tilly of Tilly and the Buttons and Rachel of House of Pinheiro who have great London fabric shopping tips on their blogs!  Even bigger thanks to B, who is the world's sweetest and most patient man!!!

An appropriate cuppa to start our last day.

Smithfield Market.  And an amazing lunch at St. John.  So yummy!!!  A place we found quite by accident on our last visit...but is now a family tradition...with Rosie making her way there during her study abroad...and an absolute must for us on this trip.  We're going to have to manage to fit this in more often, B!!!!

Buckingham Palace

Heading to the tube for our return to Heathrow and home.

But, I didn't leave empty handed!!!  Here's my fabric haul from Goldhawk Road (Shepherd's Bush).... 

  ...and this lovely selection from Walthamstow! No more fabric buying for me for some time!!!

And as if fabric alone was not enough!!!  I got patterns!!!  Most of them at an amazing Makers Fair that materialized out of thin air while we were inside Hampton Court!  As we came out to catch the train back to London...there it was!!  Fate, I tell you!  Fate!  There were food stalls with paella, curries, jams, sausages, cheese, baked goods.  We settled on The Hippy Chippy and had the best "chips" (French Fries!) ever!!!  Big tents with training sessions were available.  Other tents housed makers with soaps, jewelry, fabric, assorted crafts, and so much more.  Tilly and the Buttons and Sew Over It even had stalls!  My newest, yet to be blogged, Alder shirt dress, I happened to be wearing, was recognized as such and admired!!!!  AND...there were patterns for sale in lots of the booths!  So, I really couldn't help it!  Right, B?????

Home again...but with lots of new friends and wonderful memories.  Plus, getting back to work with my kiddos can't be too bad if this is your view along the way.

Finally, B makes my average Wednesday anything but, with a Full English Breakfast...replete with HP Brown Sauce, roasted tomatoes, beans, sausage AND bacon, toast, and perfect eggs.  B knows how to do it right!  Rosie may have to roll me around on my mat at our exercise class later today!!

Thanks, London and all the wonderful peeps who made our visit so very special.  Thanks, B.  You really don't have to spoil me so! But, it's pretty awesome that you do!  Hee hee!!! More stories to come, I promise!  Travel Chaotically!!!  I gotta go sew!!!! - love, les

Childhood experiences and PCBs relative to melanoma

This is a little weird and there is much to be considered when looking at an epidemiological study....was it strictly the point in question (here elevated PCBs), or the genetic make-up of the population, or something else they all happened to eat, drink, participate in, be exposed to????? - that makes the outcome what it is????  Nevertheless, this study caught B's eye because he knows that my grandparents and several aunts/uncles lived in this area while I was a child and young adult.  As such, I spent a fair amount of time visiting Anniston, Munford, Talledega, and Jacksonville, Alabama from early childhood until my granny passed in 1992.  I was born in 1964...so not sure what all this means or if it played any role in my condition.  For the record, no one else in my extended family who lived in that area, nor any of my siblings have melanoma, though my grandfather died of what was said to be "leukemia" though some of the information that has been passed on doesn't really line up with that, sounding more like lymphoma instead, but I was too young to understand much at the time and by the time I had a medical education there was really no way to extract more information.  However, an aunt in the area has dealt with non-Hodgkin lymphoma for about as long as I have been dealing with melanoma.  So...here you go:

Serum polychlorinated biphenyls and leukocyte telomere length in a highly-exposed population: The Anniston Community Health Survey. Callahan, Pavuk, Birnbaum et al.Environ Int. 2017 Sep 5.

Serum polychlorinated biphenyls (PCBs) have previously been associated with longer leukocyte telomere length (LTL) in most, but not all, of the few previous studies. PCBs were produced in Anniston, Alabama from 1929 to 1971 and participants of the Anniston Community Health Survey (ACHS) were highly exposed.

We evaluated serum levels of 35 PCBs and relative telomere length in 559 ACHS participants.

Relative LTL was measured in DNA extracted from blood clots. We assessed PCBs individually, grouped by chlorination, and summed PCBs. We used linear regression to assess the association between each PCB metric while adjusting for pertinent covariates.  

Serum PCBs were associated with longer LTL among white participants and the oldest age group of black participants. Among white participants, compared with those in the first quartile of sum PCBs those in the third quartile of sum PCBs had 8.09% longer relative LTL and those in the fourth had 7.58% longer relative LTL. Among African American participants, serum PCBs were associated with longer relative LTL among those over age 64 only. Tests for interaction were not statistically significant.  

We observed a non-linear positive association between serum PCBs and LTL among white participants. Serum PCBs were associated with longer LTL in the oldest age group of African Americans. This association may provide insight into the cancers previously associated with exposure to PCBs, melanoma and non-Hodgkin lymphoma, which have been associated with long LTL in previous studies.

So...if this is true, and the correlation is direct...there seems to be another need for limiting exposure to PCBs (not that we didn't already know that for numerous other reasons)!  For what it's worth. - c

LIVING with cancer. The need for psycho-social services. Pati continues to lead the way

B came upon this abstract today.  It touches on something elemental...the psychosocial aspects of a cancer diagnosis.  Having 'cancer' affects the patient, the family, everything.  We are not who we once were.  But, in the midst of trying to survive our cancer (with the simultaneous need to learn a completely new, and often foreign, cancer language - fit in doctor appointments, surgeries, radiation, oncologic therapies, manage pain and fatigue, not to mention bills and family obligations) - LIVING with cancer is a topic that is almost never addressed, while patients and their families try to soldier on with little to no psychological support or effort by institutions or medical providers to teach needed skills and coping mechanisms for the new cancer reality in which we now live.

A very dear one of mine has written:

Psycho-Oncology: A Patient's View. Garcia-Prieto P. Recent Results Cancer Res. 2018;210:57-66. doi: 10.1007/978-3-319-64310-6_4.  

Culturally the most important, valued, and less stigmatized part of cancer care is the medical part: The surgeon cutting the tumors out and the oncologist leading the strategic decision-making of the medical treatments available. The least valued and stigmatized part of cancer remains the psychosocial care. This chapter describes-through the eyes of an academic, psychologist, stage IV melanoma patient, and patient advocate-how one patient navigated changing psycho-oncological needs from early stage-to-stage IV through a whole range of psychological interventions available. Her voice joins that of all cancer patients around the world whom are urgently calling for psycho-oncological care to be fully recognized as a central part of cancer treatment.

I have tried to address this need, this world ~ many times:
2011:  Chemo Limo
2012:  My Life with Cancer
2014:  Tears and melanoma...they're not always sad...
2015:  Long term melanoma survivors....MARCH FORTH!!!!!
2015:  What to say and do....and NOT!!...for a cancer FRIEND (not patient)!
2015:  Health Monitor Magazine interview
2016:  Don't give up. Don't ever give up.
April 2017:  The Mental Price of Melanoma
June 2017:  ASCO 2017: Friends in need are friends indeed! Here's to the caregivers!!!

Yes, LIVING with cancer is not for sissies.  Luckily, we have had many advocates and dear cancer friends who, as beacons of light, have helped guide our way...even if current medical systems across the globe fail to address psychosocial needs as best they might.  Not the least of these amazing peeps is the author of the article highlighted above ~  Patricia Garcia-Prieto.

If you do not have time or interest in perusing my links above...I understand completely!!!  But, please!  Do have a peek at this one.... My Ode to Pati....a fallen comrade  especially her video, What's one life worth? [linked within].

You remain in my heart, Pati.  You continue to lead the way.  I hope your husband and sons are doing well.  love, les

I like me some shrimp!!! Now their micro-RNA can suppress the stem like qualities of some melanoma cells???!!!

Me and Bubba, man! "... like I was sayin', shrimp is the fruit of the sea. You can barbecue it, boil it, broil it, bake it, saute it. There's uh, shrimp-kabobs, shrimp creole, shrimp gumbo. Pan fried, deep fried, stir-fried. There's pineapple shrimp, lemon shrimp, coconut shrimp, pepper shrimp, shrimp soup, shrimp stew, shrimp salad, shrimp and potatoes, shrimp burger, shrimp sandwich. That- that's about it."          ~ Forest Gump

Who knew those little shrimpies could demonstrate another route through which to target and defeat melanoma?????

Shrimp miR-S8 suppresses the stemness of human melanoma stem-like cells by targeting the transcription factor YB-1.  Yang, Wei, Shang, et al.  Cancer Res. 2017 Aug 30. 

Cross-species regulation of gene expression by microRNA is a possible untapped opportunity for miRNA-based therapy. In this study, we report a novel approach to ablate melanoma stem-like cells by targeting the transcription factor YB-1, which is significantly and selectively upregulated in these cells in melanoma. Silencing YB-1 expression was sufficient to significantly inhibit the stemness of melanoma stem-like cells. In exploring YB-1 targeting, we discovered that the shrimp microRNA miR-S8 could suppress human YB-1 expression in melanoma stem-like cells. Mechanistic investigations revealed that miR-S8 recognized the 3'UTR of YB-1 mRNA and mediated its degradation. In tumor cell and xenograft experiments, miR-S8 suppressed the tumorigenic capacity of melanoma stem-like cells by targeting human YB-1. Overall, our results illuminated a novel aspect of miRNA-mediated cross-species gene expression and its use in regulating cancer stem-like cells.

Oh, yeah!!  If this works out....I'll really be like'n some shrimp!!! - c

Vitamin D and melanoma

We've long known that higher vitamin D levels provide a better prognosis in melanoma.  Here is a link (with others within) discussing Vitamin D:  Vitamin D and melanoma - folks with higher levesl do better - again!!!

Now there is this ~

On the role of classical and novel forms of vitamin D in melanoma progression and management. Slominski, Brozyna, Skobowiat, et al. J Steroid Biochem Mol Biol. 2017 Jul 1.

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)₂D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

For what it's worth! - c

Patients vs Docs: Choices in melanoma treatment

I've touched on this topic before.

Here, in Jan of this year:  Patients vs Docs - Treatment goals for cancer patients, in which researchers stated:  In our sample of 81 patients and 91 physicians, 63% of patients preferred the therapy with durable survival compared to 30% of physicians. The average patient preferred the therapy with durable survival even if the nonvarying treatment had 13.6 months longer average survival.  The presence of more severe AEs did not change these preferences.   In contrast, the average oncologist preferred treatments with fixed survival unless the survival had 7.5 months shorter average survival compared to the treatment with durable survival gains. These findings suggest patients value therapies that provide a chance at durable survival, and this result holds even when compared to therapies with more severe AEs.

Where I concluded:  Doctors should evaluate patients, explain their condition, work to find all available treatment options and present them, but PATIENTS should have the ultimate choice in the treatment they find right for them. Because it doesn't seem that docs and patients agree - and docs aren't the ones who could lose.

And here in April:   Perception....patient vs doctors in cancer care   Here, researchers noted:   "Patients place a high value on therapies that provide a chance of durable or "tail-of-the-curve" survival, whereas physicians do not. "  While my conclusion read in part:   A patient's perspective should be INCLUDED (at the very least) in their own health care decisions AND in research/trial development and implementation!!!  

Now there's this:

Patient and oncologist preferences for attributes of treatments in advanced melanoma: a discrete choice experiment.  Liu, Witt, Ebinghaus, et al.  Patient Prefer Adherence. 2017 Aug 14.

To examine and compare patient and oncologist preferences for advanced melanoma treatment attributes and to document their trade-offs for benefits with risks.

 

A discrete choice experiment (DCE) was conducted among advanced melanoma patients and oncologists. Qualitative pilot testing was used to inform the DCE design. A series of scenarios asked stakeholders to choose between two hypothetical medications, each with seven attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (MDT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to determine patients' and oncologists' choice-based preferences, analysis of variance models were used to estimate the relative importance of attributes, and independent t-tests were used to compare relative importance estimates between stakeholders.

In total, 200 patients and 226 oncologists completed the study. OS was most important to patients (33%), followed by AEs (29%) and ORR (25%). For oncologists, AEs were most important (49%), followed by OS (34%) and ORR (12%). An improvement from 55% to 75% in 1-year OS was valued similar in magnitude to a 23% decrease (from 55% to 32%) in likelihood of AEs for oncologists.

Patients valued OS, AEs, and ORR sequentially as the most important attributes in making a treatment decision, whereas oncologists valued AEs most, followed by OS and ORR. In comparison, patients differed significantly from oncologists on the importance of ORR, AEs, and PFS, but were consistent in OS and the rest of attributes.

So - when choosing treatment options, the issues in order of importance to patients were: Overall survival results, risk of side effects, overall response rates.  While oncologists considered side effects, then OS, then ORR to be the greatest priority.  Now....I could be decidedly uncharitable and assume that side effects are important to docs because if they treat patients with therapies that have fewer side effects, then they have less work to do and fewer problems to deal with!!!  But, I am not going to assume that.  What I AM going to say to oncs is this:  All treatments suck.  Melanoma can kill me if I don't get the best treatment I can.  I want to live.  And, I should  get to choose the treatment that suits MY level of tolerance for risk....NOT YOURS!!!!

Patient advocacy.  THAT is my job. - c

Sew Chaotically! - Striped Shirt Dress

I first made this shirt dress here:  Sew Chaotically! - Little denim shirt dress - Simplicity 8014!

This dress went together very well and I've made other renditions of it.  So....I decided to do one more!

I got this fabric a LOOOOOOOOG time ago, we're talking back in the 90's, with the idea of making some wide legged palazzo pants.  However, kids and college and kids and more college and work and melanoma and various other sundry events and activities intervened!!!  No worries.  Things come around.  Plus....the fabric turned out to be a FAKE!!!  After washing, the nice smooth sheen that is sometimes applied to make cheap cottons seem more luxurious washed away!!!  I was left with fabric that was much stiffer, unwieldly, more rumpled, now possessing an almost seersucker quality.  Probably not what I would have wanted in the imagined pants - but fine enough in this little dress.

No surprises in the pattern this time...as I have experienced all of them before!!  I did add length...as the original was pretty short.

I actually made the fabric belt for this version.

I can see this dress with flip flops on the beach, with tights and brogues, or boots and a jacket in cooler weather.

One more piece in the stash, turned into a useful garment!!!

Another example demonstrating that spending a bit more on "good" fabric, can be sewwwwww worth it!  I live and learn!!!  Sew Chaotically!!! - les

T-VEC (Talimogene laherparepvec, Imlygic...whatever you want to call it) - oncolytic virotherapy may improve the efficacy of anti-PD-1 by changing the tumor microenvironment!!

Those of you who have hung around this site for more than ten minutes know I have long been yelling about the benefits of intralesional/intratumoral therapies, especially when combined with systemic thereapies.  This synopsis of the latest ASCO report covers much of the data:  ASCO 2017: All things intralesional/intratumoral

Now there's this:

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Ribas, Dummer, Puzanov, ...Hodi, Long. Cell. 2017 Sep 7.  

Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8⁺ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8⁺ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. 

The more we know....  Hang in there, ratties!!!  - c

Nivo better than ipi as adjuvant treatment for melanoma! Surprise, surprise, surprise!!!

For those of you who don't know...back in 2010 I joined 33 other ratties with resected Stage IV melanoma in a trial of nivo (with peptide vaccines that did NOT help).  I had had 2 cutaneous lesions, a positive node, went on to have a resected lung met, SRS to a brain met, and surgery for a tonsilar met, but was NED at entry to my trial.  There were 30 ratties in an advanced melanoma arm as well. Eventually that trial morphed into many, many different arms to include:  folks with prior use of ipi, to stop requiring the vaccines and HLA positive typing, the ipi/nivo combo and all sorts of things.
However, here are the results of my NED 33:  C'est moi!!! Results from the 33 ratties in my Nivolumb/Opdivo trial...published!

With my thoughts:  My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...
FYI:  I was treated with only 1mg/kg of nivo, every 2 weeks for 6 months, then every 3 months for 2 more years.

Now there is this:

Adjuvant Nivolumab vs Ipilimumab in Resected Stage III or IV Melanoma. Weber, Mandala, Del Vecchio, et al. NEJM. September 10, 2017.

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.

In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population.

At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% in the nivolumab group and 60.8% in the ipilimumab group. Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment.

Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab
Here is a link to the full article:  Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. Weber, et al. NEJM

So here's the deal:

Stage IIIB, C, or Stage IV melanoma patients were allowed...even those with brain mets...as long as all were completely resected.

Patients joined from March 2015 to November 2015

There was a 5% cutoff for PD-L-1 staining (ie positive for PD-L-1 staining on tumors)

Nivo was given at 3mg/kg every 2 weeks or ipi was given at 10/mg/kg every 3 weeks for 4 doses then every 12 weeks.  Either drug was given for one year.

Patients were assessed via CT's of body and MRI of the brain every 12 weeks for 2 years, then every 6 months until year 5.

905 patients were studied, none of whom were still getting the drug by the final report.

Only 397 of these patients completed the full year of drug treatment.

Of the 452 in the nivo arm, 275 completed the year.  Of the 453 in the ipi arm, 122 completed.

Nivo outcomes were better than ipi no matter the patient's age, sex, disease stage, or BRAF status.  Nivo had fewer side effects.

In prior studies, ipi has demonstrated a pretty consistent 60% recurrence free survival in Stage III NED patients when used as adjuvant.  That number held in this study even when Stage IV patients were included.

Recurrence free survival at 12 months:

70.5% for nivo                    60.8% for ipi

Recurrence free survival at 18 months:

66.4% for nivo                    52.7% for ipi

Median distant metastasis free survival was not reached in either group.  However, it was longer in the nivo group with mets developing in 93 of the 369 peeps in the nivo group and in 115 of the 366 ipi group.

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.

Back to me and my ratties, as of September 2015...of the 33 Stage IV ratties enrolled, only 10 of us had relapsed.  That is a recurrence free survival percentage of 69%....but with longer time out from treatment.  Interestingly, in my study....only 2 of the 10 brain met patients had relapsed.  

Here is that post:  9/11/2015: Latest update on my Nivo/Opdivo study peeps and me...

And finally, I am asked at least weekly by someone via email, MPIP, or my blog...

"So, when will I be safe?  If I make it out 1 year (2, 3, etc) I'll be free of melanoma, right????"

That is the zillion dollar question if you are lucky enough to have made it this far, isn't it?  Sadly, it is one that we do not yet have an answer to....though we ratties are doing our best to give you some great numbers with the treatments at hand.  

Here is one such discussion with references to other arms developed in my study:  9 months after Nivolumab trial...stats, f/u, what we learned....  

I have listened to B and Weber discuss Kaplan Meier curves until I thought my brain would develop ANOTHER tumor!!!  B arguing for 2 years being the point they flatten out....Weber hedging his bets and noting 3 years as that magical point.  Bottom line:  Every day out is one day better.  Researchers agree now, pretty much across the board, that one year out with no disease is great, 2 years out is amazing and 3 years out there is a plateau which may mean....a CURE!!!!    We shall see.  Melanoma is a sneaky bitch.  However, every day forward is another day.  Another day to live and enjoy. Another day down the road to a cure....whether via current treatments already attained...or even better ones that may save even more dear ones.

Here's to the ratties!!! - les

Sew Chaotically! -Tessuti Mandy Boat Tee - for Edster!!!!!

Okay, Ed!!  You, too, can become a sewist and this is an easy, but sartorial choice to begin with!!! AND...the pattern is FREE!!! You can download it here:  Free Sewing Patterns from Tessuti! 

The only tricky thing about this pattern is that it is "one size fits all". Seems easy enough, right?  But, it also seems a little unlikely....unless you want it to look as though you and everybody else could fit in it!!!  I perused various sewing posts to figure out the fit.  I found these to be the most informative:

This one, from the Tessuti site itself, explains what went into making three different versions:  Tessuti - Classic Mandy Stripes
And this one, from Danielle, who is just about my height and size with a cool blog, addresses 3 Mandy tees as well:  Sewing and Cocktails - Mandy

Don't get me wrong.  This is supposed to be a loose boat neck tee and I had no intention of trying to turn it into anything else.  However, there's loose and there's looking like you are wearing a bed sheet. I wanted to hit somewhere in the middle.  Additionally, many, many reviews noted that the neckline was quite high and the sleeves were very snug.  Now, my arms are not huge, but I didn't want to have them look as though they were sausage wanna-be's, nor diminish normal range of motion.  So...taking all the various comments and measurements into account....here's what I did.

I started with a super soft and drapey rib knit from JoAnn's and given what I'd learned, knew I was going to need to take out some of the fabric in the bodice of the shirt.  The Tessuti link recommended pinching a bit (in her case 3.5 cm..I think) from the center and since the front and back pieces are cut on the fold that would have been the easiest solution.  However, since then you have to worry about having made the neck opening too small, I opted to remove 3 cm from both the front and back pieces at the shoulder...just past the neck opening.  I figured with the dropped shoulder, it wouldn't hurt anything and I could just extend the sleeves.  I wanted to keep this a boatneck, but I didn't want to feel like Snoopy on a leash either, so I took a small crescent (1/2 inch at the center neck, curving to nothing at the end of the neck opening) from the front piece only, leaving the back alone.  I also opened the pattern piece for the arm straight up the middle, leaving the shoulder attached like a hinge, to increase the diameter of the lower arm by about 1/2 inch.  I adjusted the sleeve length to fall where I wanted it...taking the dropped shoulder into account.  Once back, front, and arms were attached, but the arms and sides still waiting to be stitched - I cut another inch from both the bodice sides while the shirt was laid flat. Given the 'flimpy-ness' of my fabric, I did reinforce the shoulder seam with stay tape and used knit fusible tape at the neck, sleeve and waist hems.   Seams were stitched with my serger.  The hems were done with a double needle on Bernie!

That seems like quite a lot of effort when you have a pattern, but...it really wasn't that bad once I got my head wrapped around what I was actually going to do!

I think I left plenty of room in the bodice and am really glad I gave myself a smidge more space for my super jacked arms!!!  I'm glad I didn't mess up the neckline, as that was the main allure to this pattern for me from the start!  (Check out that stripe matching, Bentie!!!)

I like my Mandy!!!  Thanks, Tessuti!

Okay, Ed!  You got this.  I bet you've got some chicas in your world who would just love a Mandy!!! Sew Chaotically!!! - les

EXCELLENT presentation on how our immune system works (or doesn't) in melanoma!!!!!

Great thanks to my Edster who shared this video link!!!  It is a really great presentation by Dr. Weber about how our immune system works generally, how melanoma uses its Potter-esq 'invisibility cloak' to hide from our immune system, the development of immunotherapy, ipi, progression of melanoma followed by regression while on immunotherapy, crazy side effects created, anti-PD-1 and it's specificity with fewer side effects and better response rates, the ipi/nivo combo, and additional combo's as a way to improve future outcomes:

Immunotherapy for Melanoma: Presentation given by Jeffrey S. Weber, MD, PhD, as part of the AIM at Melanoma’s Patient & Caregiver Symposium on April 8, 2017 at NYU Langone Medical Center in New York, NY. Dr, Weber is a Professor, Department of Medicine at Perlmutter Cancer Center.

Definitely worth a look and a listen!!!  Stories I've heard before in person.  And, I can't begin to tell you how many times I've heard, "This stuff is weird!"  A completely understandable pronouncement when discovering all the bits and pieces of anti-PD-1 therapy!  A little disconcerting when you are the rattie in the gown on the table!!!  None-the-less, I remain ever so grateful to the ratties who went before me, my super-duper support team, and The Wizard Weber!!!!

"The best is yet to come...." ~ les

Trial results from the use of the Ipi/Nivo in NED melanoma patients

Back in 2010 I was one of first 10 folks who made up the 33 melanoma participants in the Stage IV NED arm of a nivolumab (now called Opdivo) with peptide vaccines (They did nothing!!!  Here's that story: Peptide vaccines do NOT trigger effective immune reponse to melanoma!!!! Of mice and men....) phase 1 trial.  Our NED arm was compared to folks with active disease.  Ten NED peeps, and 10 with active disease, were given Nivo at 1mg/kg.  Later, since we didn't die or grow three heads, 10 more NED, 10 more with active disease were treated with nivo at 3mg/kg. Finally, 10 more were added to each arm , this time at 10 mg/kg.  We were all treated until progression or significant side effects, for a max of 2 1/2 years.
Here are the results, published in 2014, of my NED arm:  C'est moi!!! Results from the 33 ratties in my Nivolumb/Opdivo trial...published!
Here is a related post:  My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...

That trial morphed in all sorts of directions!  Arms were added that stopped giving the vaccines after we learned they were worthless. Important in that those peeps got to avoid the torture of the vaccines and in that it opened the trial to many more folks as the HLA typing required for the vaccines no longer limited participation.  Arms were created for folks who had already been treated with ipi. Additional arms gave the ipi/nivo combo to folks with active disease as well as those who were NED.

Having recently completed my annual scans, I duly contacted the person still managing the trial at Moffitt along with Dr. Weber and gave them the results.  Hell, if I'm gonna be a rattie....I want the data to be followed!!!!!!!!!!!!!!!
The latest data I had was this from 2016:   Udate on me and my ratties...from my 2 1/2 year, 2010 Opdivo/peptide vaccine trial at Moffitt - anti-PD1 as adjuvant. where I quoted:  The tote is that [there were] only 7 deaths in 33 patients with no deaths this year.  Only 2 deaths in the 40 subsequent patients.  Great record!"
And wrote this:  So there you have it, folks.  From the wizard himself.   These were 73 Stage IV melanoma patients, rendered NED via radiation and surgery, then treated with nivolumab (Opdivo).  Though we have sadly lost 9 of our tribe of ratties, many of us have now lived 6 years post that diagnosis.  Way past our previously expected shelf life!  Anti-PD1 products SHOULD be available to Stage III/IV NED patients, should they wish to use it.  We ratties have fought to prove its value! 

I asked for any up-dated info on my rattie peeps from the manager at Moffitt.  Don't know if that request was lost in translation, or if there just hasn't been any more tabulated, but the following is what she sent me:

Adjuvant nivolumab (NIVO) plus ipilimumab (IPI) for resected high-risk stages IIIC/IV melanoma (MEL).

Nikhil I. Khushalani, Youngchul Kim, Geoffrey Thomas Gibney, Ragini Reiney Kudchadkar,Zeynep Eroglu, Joseph Markowitz, ... Maria P. Czupryn, Melissa S. Thebeau, Lori McCormick,Allison Richards, Jeffrey S. Weber Journal of Clinical Oncology, May 2016

Background: Patients (pts) with resected stage IIIC or IV melanoma are at very high-risk for recurrence and effective strategies for adjuvant therapy are needed. Combination NIVO + IPI yields high response rates but has a high rate of grades (G) 3-4 toxicities in advanced MEL. We examined the safety and efficacy of 2 dosing schedules of NIVO + IPI in resected stage IIIC and IV MEL pts. Methods: Resected stage IIIC/IV MEL pts who were free of disease, with adequate laboratory indices and performance status of 0-1 were treated with NIVO (1mg/kg) + IPI (3mg/kg) Q3 weeks X 4 doses (induction) followed by 2 years of NIVO at 3mg/kg Q2 weeks (Cohort A). Toxicities observed during induction led to opening of cohort B consisting of NIVO (3mg/kg) + IPI (1mg/kg) Q3 weeks X 4 doses followed by the same maintenance. Pre-defined criteria permitted initiation of NIVO maintenance following recovery from induction toxicity in both cohorts. Results: Twenty pts were treated in each cohort. Median age was 50 (22-78) in cohort A and 55 (29-77) in cohort B; stage IIIC pts constituted 65% and 60% of the respective cohorts. Toxicity precluded completion of all 4 induction doses in 50% in cohort A (most common was G3-4 ↑ AST and/or ALT in 7 pts) and 35% in cohort B. The most common G3-4 toxicities (minimum 5 events) are listed in the table. Hypophysitis developed in 28% (7 pts in cohort A). The incidence of ↑ AST/ALT, nausea, anorexia, cough, weight loss, neurotoxicity and endocrine toxicity was significantly higher in cohort A. In this group, 5 pts (25%) completed all induction doses and remain on NIVO maintenance; in group B, this number was 40%. There have been 4 relapses in cohort A, and 3 in cohort B. Only 1 pt in this high-risk study group has succumbed to MEL recurrence. At median follow-up of 21.3 months and 11 months respectively for the two cohorts, the median progression-free survival and overall survival have not been reached. Conclusions: In very high-risk resected MEL, adjuvant NIVO + IPI followed by maintenance NIVO has encouraging activity. Dosing per cohort B appears better tolerated and warrants further study.

So...not really 'new' as this was published in 2016 and not exactly what I was looking for as it is not from my cohort.  But....given the continued paucity of treatments allowed, other than ipi, for high risk NED melanoma peeps..and the good outcomes demonstrated...I thought it was worth sharing.  Hang in there ratties.  We're getting there!!!
P.S.  Will post any updated data specific to my ratties if I get it. - c