Tuesday, September 19, 2017

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 physicians63% 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

Monday, September 18, 2017

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

Friday, September 15, 2017

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

Tuesday, September 12, 2017

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.  

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

Saturday, September 9, 2017

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

Thursday, September 7, 2017

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

Wednesday, September 6, 2017

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).
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