50 IS nifty!!! Happy Birthday Ruthie!!!!

Frankie had a wonderful idea and carried it off!!!  He got almost all of Ruthie's peeps to meet in B'ham to celebrate her birthday.  Shhhhhh......  It's a surprise!!!

Having gotten there a bit early, Rosie and I had fun exploring the fashions and ridiculous prices of Saks Fifth Avenue.

Look at my me-made Paris Dress flow in the breeze as we head toward our meeting place!

Surprise!!!

I think she was!!!!

Hee hee!!!

Me plus Ruthie....and THIS happens!!!

Amazing gift...

...also me-made....

....of wood...from Carla!!!  The girl's got skillz!!!

Cause the photog is weird and well....awesome shoes!!!  Plus Ruthie's dress!!!

Also a me-made!  By her!!!  You should see the things SHE sews!!  Beautiful!

Cause at 50 you deserve a BE-UUUU-TE-FULLY wrapped gift!  Hee hee!

Sisters in the house!

You're a good man Frankie!!!!

Awesome boys!!!  Love you Char and Sha!!!!!

Yummy lunch!!  You rock, Frank!

Looking normal...

...then this happens...

...then this!!!  Can't explain it!

Photog made it in the pic!  Thanks, stranger!

 Happy, happy day, Ruthie!!!  Thanks to all of you for great fun!  Here's to many more!!! - les

Melanoma antigens in blood are prognostic of OS and correlated with response to ipi!

I've talked about biomarkers before.  Here's a post from earlier this year (with additional links within - including one to another study that found blood biomarkers associated with response to ipi):  Biomarkers - blood components, circulating tumor cells AND of the tumor itself 

A valid and specific blood draw that could help diagnose, determine the presence of a response to therapy, and be used as follow-up (instead of scans!) would be sooooooooooo  awesome!!!!  Now there's this:

Melanoma antigens are biomarkers for ipilimumab response.  Arenberger, Fialova, Gkalpakiotis, et al.  J Eur Acad Dermatol Venereol. 2016 Aug 24. 

Novel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA-4-blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed.

To determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab.

Patients (n=62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of 4 melanoma markers on circulating cells Melan-A, gp100, MAGE-3 and MIA prior to the treatment and within the therapy were compared to the data collected at baseline - after the melanoma surgery.

The immunotherapy pretreatment marker level was found to be prognostic of overall survival, lower levels were linked to longer survival time. Moreover, longitudinal follow-up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by greater than 30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumor markers during the treatment precedes clinical progression and gives an early warning of treatment failure. 

Melanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy.

Come on researchers.  Let's make this happen!  Soon!!! - c

Happy anniversary, baby.....

....got you on my ~ mind!!!  Twenty eight years????  OMG!!!!  Two kids, 4 dogs (6 if you count Lucy and Clown!), 2 apartments, 3 houses, lost count of cars and hamsters, buckets of tears, loads of laughter (Cause you know I'm funny!!!), 13 years of melanoma (Now, that's been fun!!!), a bazillion patients, dear friends, foreign lands, lots of 'Spranch', crazy travels, fun dinners, gardens of flowers....hmmmm....

Some weird doc I know, along with a real live radiologist, pronounced me melanoma free late yesterday.  So listen to this...I guess I'll die, another day!

I'm gonna wake up, yes and no
I'm gonna kiss some part of
I'm gonna keep this secret
I'm gonna close my body now
I guess I'll die another day
I guess I'll die another day

Sigmund Freud
Analyze this
Analyze this

I'm gonna break the cycle
I'm gonna shake up the system
I'm gonna destroy my ego
I'm gonna close my body now

I think I'll find another way
There's so much more to know
I guess I'll die another day
It's not my time to go
For every sin, I'll have to pay
A time to work, a time to play
I think I'll find another way

It's not my time to go! ~ Madonna ~ Die Another Day

Guess you're stuck with me a bit longer! Ready for 28 more?????? love, les

Sentinel lymph node disection ~ "important diagnostic procedure and might be of therapeutic benefit re: DFS and OS!"

I have long said that sentinel lymph node removal and testing in melanoma seems like a complete no-brainer to me!!!  It is done when you return for the needed wide excision around the tumor that was removed.  It is minimally invasive considering you're going to have the wide excision anyway.  It is the only way to know what stage you really are.  You may have only cutaneous disease and therefore are categorized as Stage 1 or 2....based on how thick your lesion was, the presence of ulceration, etc.  BUT....if you have a positive node to go with that....you are then Stage 3....and that is a very different place to be.  

1.  It's important to know that's where you are in melanoma land.

2.  It makes a world of difference in recommended follow up.

3.  It makes a world of difference in what insurance companies will cover for your follow-up.

4.  AND....it makes a world of difference in potential treatment options.

Here is a post from 2013 with some articles discussing the odds of having a positive node:  With melanoma, you can never be too rich or too thin!

Here is a post from this year, with several links within, addressing risks for positive nodes in females specifically:  Women and melanoma risk

NOW....do NOT confuse sentinel node removal and biopsy with a complete lymph node dissection (CLND).  CLND is different.  A CLND is when, usually after having one or more positive nodes, all the lymph nodes are removed from the nodal basin (the area in which the positive node was located).  This IS invasive surgery and has the potential to cause nerve damage and or lymphedema, among other things.  IF you had a positive sentinel node...this would be one of the things you would have to decide about doing or not.  The science and data surrounding whether this is helpful or not, worth the potential damage or not, is murky.  There are studies that say it helps and others that say is does not.  BUT whichever way you decide to go with this...this is a decision made AFTER the sentinel node dissection and separate from it!!!

Here's a post showing three studies addressing the issue:  "Patients with microscopically negative/PCR+ SLN have increased risk for nodal recurrence that was mitigated by CLND"! 

Now there is this:

 

The impact of sentinel node dissection on disease-free and overall tumor-specific survival in melanoma patients: a single center group-matched analysis of 1,192 patients.  Geimer, Sattler, Flaig, et al.  J Eur Acad Dermatol Venereol. 2016 Aug 24.

Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence removal of potential lymph node micrometastasis will alter survival outcome.

The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus sentinel lymph node dissection (SLND group) to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma.

A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumor thickness and localization of primary tumor. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in and hence subject to change over time.

Kaplan-Meier testing revealed significant differences in survival in favor of the SLND group. Mean overall tumor specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group, respectively. Disease-free survival (DFS) and time to lymph node progression also differed significantly between the two groups.

SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumor-specific survival of melanoma patients.

See what I'm saying?  Nothing in melanoma is easy. Absolute therapeutic effect of SLND may not be that impressive, though still a positive in this study, but SLND seems rather essential for diagnostic purposes.  At least this part seems pretty clear to me.  Good luck to all of you and whatever you decide.  - les

Sooo....MRI for tomorrow....approved...just now!!!! This afternoon!

Have I mentioned how much I hate insurance companies?  Oh, yes.  I have.  But, really!!!   I HATE insurance companies!!!  As I mentioned previously....normal (except....NOT normal...cause all us melanoma brain and lung met peeps used to die in short order!!!), ANNUAL (Like...shouldn't we be celebrating?????) follow up CT's of neck, chest, abd and pelvis with MRI of brain were ordered by my oncologist.  MRI = DENIED...so decreed Michele Awobuluyi, MD of Blue Cross Blue Shield, cause after 5 years with my "Stage 2 to 4 skin disease" I don't need them any more, don't you know???!!!  Per the insurance demands, I saw my oncologist, BEFORE getting the scans.  A waste of my time and hers.  A waste of my copay.  A waste of BCBS money.  Because....until I get my scans, we don't really know what we are dealing with now do we?  My doc appealed Dr. Awobuluyi's decision.  DENIED!!!  So today....after my doc did a "peer to peer petition"  (Now, that's a joke isn't it?  Peer to peer?  Seriously?  Normal, average docs, with 2 brain cells would not categorize metastatic melanoma as "skin disease"!!!  So, my onc is no peer of Dr. Awobuluyi!!!) Finally - BCBS has, in all their wisdom, authorized the MRI of my brain.  This afternoon.  For an MRI scheduled for tomorrow!  Can you say A$$ HOLE$?????

Yet, I'm sure they think I should be ever so grateful. Sorry.  Rant over.  For now.  I am in a much luckier position than many.  #firstworldproblems.  Still....  Now you all know what I'll be doing tomorrow!!!!  Think I'm gonna just sit and look at my cute shirt for a minute while taking deep cleansing breaths!!!! - c

Sew Chaotically! - Vogue 1440 - such a cute top!!

Another sewing post...just for fun!!!  Here's the pattern.  I have to say...from looking at the directions and pieces...the jacket could easily turn into a hot mess...but the top...

...how cute it that back??????

Material...from who knows where and sadly when!  When she was little, I used to pick up anything "rosebud" for the Rose Bud...though clearly, this never made it into her wardrobe!!!  I was going to pair it with a pink I had, but the Brentster, with his incredible color skills picked this combo!  Awesome, right?

Hey, if you have a cute design....make it show up, right????

Made a size 12, just had to carve a bit off both side seams.  Didn't want to mess with the substantial darts running down the front!

Proud of my top stitching!!!!

Lurve it!!!  Happy day to you...even if it sneaks up on you from behind! - c

Anti PD-1 and Anti-PD-L1 treatments rarely confer durable remissions for metastatic uveal melanoma (and poor responses in acral and mucosal mel as well!)

As many of you know, I am frequently contacted by folks with melanoma (or those with peeps who are suffering) looking for answers, treatments, explanations.  I help as best I can.  In that capacity, I have discovered many who are facing more than just cutaneous melanoma and are gradually coming to realize that they or their loved one, is probably dealing with uveal, acral, or mucosal melanoma given the history, location, or results of testing.  Unfortunately, while we have made a great deal of progress since 2011 in the treatment of melanoma generally, these sub-types are notoriously unresponsive to the now conventional melanoma treatments.  For instance, this is a report out of ASCO this year: ASCO 2016: Anti-PD1 for acral and mucosal melanoma , where unfortunately it was demonstrated that rather than the more typical 40% response rate to anti-PD1 in treatment naive cutaneous melanoma, folks with acral melanoma had only a 32% ORR, while folks with mucosal attained only a 23% ORR....albeit these peeps were heavily pre-treated and perhaps that contributed to the lower response rates as well.
  
Additionally, these types of melanoma are less likely to be BRAF positive, removing yet another treatment option from their arsenal.  Here's data from a discussion between two melanoma specialists:  Pick your poison: Weber and Agarwala discuss combination therapy for melanoma
Here they note the following expected mutation rates -
Mucosal = 9% BRAF, 12% NRAS, 25% KIT
Acral = 22% BRAF, 16% NRAS, 24% KIT

The disconcerting aspect for me has been this response, "Oh, no.  We aren't [or - the doc isn't] calling it that! If that happened, she wouldn't be eligible for the trial!!"  I can hear the fear and desperation in their voice.  I really do understand!  I spent many years, even as a Stage IV patient, in melanoma land BEFORE the FDA approval of the BRAF inhibitors, anti-PD1, or ipi. I fully recognize the desperation and search for an effective treatment.   However, when you are allowed placement into a trial or treatment that we now KNOW provides little to no benefit for your particular mutation....what has been accomplished?  To my mind, time has been wasted, suffering continues, while other possibly more effective options go untapped.  Some Melanoma Big Dogs recently came together in this report regarding uveal melanoma response rates to anti-PD1 and anti-PDL1:

Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-1L antibodies.  Algazi, Tsai, Shoushtari, ... Daud, Sosman, Carvajal, Chmielowski, Postow, Weber, et al.  Cancer. 2016 Aug 17.

Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized.  Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively determined.  Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty-eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in 2 patients for an overall response rate of 3.6%. Stable disease (greater or = to 6 months) was observed in 5 patients (9%). The median PFS was 2.6 months, and the median OS was 7.6 months. There was no association between prior treatment with ipilimumab or liver-directed therapy and PFS or OS. Treatment was well tolerated, and only 1 patient discontinued treatment because of toxicity.  PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population.

A sad acknowledgement to be sure.  These response and OS rates are really no different than those I was facing prior to the existence anti-PD1!  Frustrating and powerless do not begin to cover the feelings that this data engenders!!!  However, it is something I would want to know, if I were dealing with uveal melanoma.  For what it's worth.... - c

Titanium....

Rough day....rough week.  More for others than myself. Just when I think it is too much....I know....I am titanium...

Sia/David Guetta - Titanium

You shout it out,
But I can't hear a word you say
I'm talking loud, not saying much
I'm criticized but all your bullets ricochet
Shoot me down, but I get up
I'm bulletproof, nothing to lose
Fire away, fire away
Ricochet, you take your aim
Fire away, fire away
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
Cut me down
But it's you who'll have further to fall
Ghost town and haunted love
Raise your voice, sticks and stones may break my bones
I'm talking loud not saying much
I'm bulletproof, nothing to lose
Fire away, fire away
Ricochet, you take your aim
Fire away, fire away
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
I am titanium
I am titanium
Stone-heart, machine gun
Firing at the ones who run
Stone heart loves bulletproof glass
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
You shoot me down but I won't fall
I am titanium
I am titanium                        ~ David Guetta

...and so are you.  Love, c

Immunotherapy and pneumonitis

I am certain I dealt with pneumonitis while taking nivolumab/Opdivo for 2 1/2 years in my trial.  I noted this back in the day:

Dose 7 = 3/25/2011
   My scans at the 3 Month evaluation showed "ground glass appearance" in the right lower lobe of my lung.  I was also having wheezing at the time.  Scans were reviewed by the tumor board at Moffitt and determined to be related to my asthma or an inflammatory process that Weber had seen before in patients on ipi.  Wheezing gradually improved on albuterol and inhaled corticosteroid; symbicort. Perhaps most importantly, the 3mm something???? in my brain on my MRI when I started is GONE!

Additionally, when reviewing my records (created in this blog!!!) it was very clear that my infusions were directly followed by bouts of wheezing. It never got so bad that I had to stop my infusions or required systemic steroids, though my nurses often threatened me with them!  I dealt with my wheeze using albuterol as well as inhaled steroids (symbicort or pulmicort).  My history is a little hazy given my asthma and my work with little germy critters, but as B recently told my local onc, "Celeste, definitely experienced pneumonitis.  But, she and Weber are tough as nails, so they just powered through!"  And, as noted above, my scans were at one point read as having a "ground glass appearance"...the classic radiologic description for pneumonitis....but that's not always how pneumonitis rolls, as this latest article indicates: 

PD-1 inhibitor-related pneumonitis in advanced cancer patients: Radiographic patterns and clinical course.  Nishino, Ramaiya, Awad, ... Hodi, et al.  Clin Cancer Res. 2016 Aug 17.  

The purpose of this study was to...investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.  Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.  Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy and 15 received combination therapy. Median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. AIP/ARDS pattern had the highest grade, followed by COP, while NSIP and HP had lower grade. COP pattern was most common in all tumors and treatment regimens. Most patients (17/20;85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; two of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.  PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients.

(Found this article as well....so it is being added as a late addition to this post...)

Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.  Nishino, Giobbie-Hurder, Hatabu, Ramaiya, Hodi.  JAMA Oncol. 2016 Aug 18.

Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.  To compare the incidence of PD-1 inhibitor-related pneumonitis among different tumor types and therapeutic regimens.  A PubMed search through November 10, 2015, and a review of references from relevant articles. For the PubMed search, the following keywords or corresponding Medical Subject Heading terms were used: nivolumab, pembrolizumab, and PD-1 inhibitor.  Twenty-six original articles of PD-1 inhibitor trial results were identified. Among them, 20 studies of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) were eligible for a meta-analysis.  The data were extracted by 1 primary reviewer and then independently reviewed by 2 secondary reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparisons of the incidence were based on marginal, exact generalized linear models with generalized estimating equations.  Incidence of all-grade and grade 3 or higher pneumonitis and pneumonitis-related deaths.  Twenty studies of single-tumor-type trials of PD-1 inhibitor (12 melanoma studies, 5 NSCLC studies, and 3 RCC studies) (a total of 4496 unique patients) were included in the meta-analysis. The overall incidence of pneumonitis during PD-1 inhibitor monotherapy was 2.7% for all-grade and 0.8% for grade 3 or higher pneumonitis. The incidence was higher in NSCLC for all-grade (4.1% vs 1.6%) and grade 3 or higher pneumonitis (1.8% vs 0.2%) compared with melanoma. The incidence in RCC was higher than in melanoma for all-grade pneumonitis (4.1% vs 1.6%) but not for grade 3 or higher pneumonitis. Four pneumonitis-related deaths were observed in patients with NSCLC in the monotherapy group. Pneumonitis was more frequent during combination therapy than monotherapy for all-grade (6.6% vs 1.6%) and grade 3 or higher pneumonitis (1.5% vs 0.2%) in melanoma, with 1 pneumonitis-related death during combination therapy. Multivariable analyses demonstrated higher odds of pneumonitis in NSCLC for all-grade and grade 3 or higher pneumonitis and in RCC for all-grade pneumonitis compared with melanoma. The combination therapy had significantly higher odds than monotherapy for all-grade and grade 3 or higher pneumonitis. The incidence of PD-1 inhibitor-related pneumonitis was higher in NSCLC and RCC and during combination therapy. These findings contribute to enhance awareness among clinicians and support further investigations to meet the clinical need.

Nothing is ever simple when dealing with melanoma, its treatments, or their side effects!!!!  If you have a wheeze or cough...talk to your doc!!!  Hang in there melanoma peeps!! - c

Medical studies in children go unpublished!!! Here we go AGAIN!!!

Back in 2013 I wrote this post from a study that noted:  Almost 50% of results of cancer drug trials NOT unpublished!

What the tub?????????  And now this report notes that 19% of studies involving our most fragile population, CHILDREN, are not completed and 30% of those that are, go unpublished!!!

In this report recently on NPR Medical studies involving children often go unpublished reporter Richard Harris notes:

Many medical studies involving children never end up being put to use because scientists frequently don't publish the results of their work, according to an analysis published online Thursday.
The findings raise both scientific and ethical issues regarding research on this vulnerable population.
Previous studies have documented that about a third of all clinical trials conducted in the United States end up as largely wasted effort, because the scientists doing that work don't take the effort to publish and share their results with the scientific community.

[In the study by Bougeois and Pica, Pediatricians at Harvard and Boston Children's Hospital published in the journal] Pediatrics, the experience with childhood research is just about as bad.
The report, reviewing clinical trials started in 2008-10, finds that 19 percent of the studies that recruited children didn't run to completion. That was often because researchers weren't able to recruit as many volunteers as they needed to run the experiments. And of the 455 trials that were completed, the results from 30 percent weren't published.

"That means all the participants who are enrolled in these studies aren't able to contribute in a meaningful way to our clinical information and knowledge," Bourgeois said. One reason may be that scientists didn't get the results they were hoping for. It's less rewarding to publish results that report a failed trial, but Bourgeois says it's just as important for science to do so.

"The harm is we end up with scientific literature that only shows all the things that do work," she said. "It may falsely appear that certain interventions do work. So our literature may become biased and may not be representative of the true efficacy or safety of an intervention."  One result of that is that other scientists may try to run the same failed experiment, and end up down the same blind alley as scientists who had tried it before. "That leads to a lot of inefficiency and waste," she said.  Parents volunteer their children for these studies with an understanding that their efforts are contributing to the advancement of medical science.

The shortcomings of pediatric research come as no surprise to Dr. Joseph Ross [Yale School of Public Health]. He arrived at similar results when he analyzed clinical trials that include adults. Scientists have many explanations for why they don't publish their results. "Maybe the results don't show what the investigator wants and they move on," Ross said. "But more often people are busy and people don't focus enough time and attention on getting those results out."  Ross considers this an ethical lapse. "When you do a clinical study and you're asking patients to participate and subject themselves to a risk, in order to inform science and generate knowledge, you have an ethical obligation to disseminate those results to the wider scientific community," he said.

While clinical trials are necessary and can save lives, there are many, many problems that need to be fixed and publication of data is certainly one!!!  Here's my oped (as it were) from earlier this year:  The Problem with Clinical Trials

However, I am holding out hope.  I recently noted:  Most excellent news! Biden threatens to cut funding if cancer trials conceal results!!!  Let's go, Joe!!!!!!!!!!!!! - c

coBRIM trial (cobimetinib wih vemurafenib) - updated results

I reported on this combo first back in 2014:  BRAF/MEK combo: vemurafenib with cobimetinib

Then this also in 2014:  Combination therapies for melanoma (with some cool graphs)

Here in 2015 with the FDA approval:  Two new FDA approvals for the treatment of melanoma

 

And this was out of ASCO this year: ASCO 2016: cobimetinib and vermurafenib

Here is the latest update:

Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.  Ascierto, McArthur, Dréno, Chang, Ribas, et al. Lancet Oncol. 2016 Jul 29.  

The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF^V600-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated efficacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies.  In this double-blind, randomised, placebo-controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAFV600 mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily). Progression-free and overall survival were primary and secondary endpoints, respectively; all analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01689519, and is ongoing but no longer recruiting participants.  Between Jan 8, 2013, and Jan 31, 2014, 495 eligible adult patients were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib group (n=248). At a median follow-up of 14·2 months, the updated investigator-assessed median progression-free survival was 12·3 months for cobimetinib and vemurafenib versus 7·2 months for placebo and vemurafenib. The final analysis for overall survival occurred when 255 (52%) patients had died (Aug 28, 2015). Median overall survival was 22·3 months for cobimetinib and vemurafenib versus 17·4 months for placebo and vemurafenib. The safety profile for cobimetinib and vemurafenib was tolerable and manageable, and no new safety signals were observed with longer follow-up. The most common grade 3-4 adverse events occurring at a higher frequency in patients in the cobimetinib and vemurafenib group compared with the vemurafenib group were γ-glutamyl transferase increase (36 [15%] in the cobimetinib and vemurafenib group vs 25 [10%] in the placebo and vemurafenib group), blood creatine phosphokinase increase (30 [12%] vs one [less than 1%]), and alanine transaminase increase (28 [11%] vs 15 [6%]). Serious adverse events occurred in 92 patients (37%) in the cobimetinib and vemurafenib group and 69 patients (28%) in the vemurafenib group. Pyrexia (six patients [2%]) and dehydration (five patients [2%]) were the most common serious adverse events reported in the cobimetinib and vemurafenib group. A total of 259 patients have died: 117 (47%) in the cobimetinib and vemurafenib group and 142 (58%) in the vemurafenib group. The primary cause of death was disease progression in most patients: 109 (93%) of 117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 in the vemurafenib group.  These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a standard first-line approach to improve survival in patients with advanced BRAF^V600-mutant melanoma.

And as one would assume....progression free survival as well as median overall survival was greater when vemurafenib was combined with cobimetinib than when it was given with a placebo.  Perhaps a little surprising was the fact that side effects were higher in those receiving the cobimetinib and vemurafenib combo, as the BRAFi/MEKi combo's are generally shown to have greater efficacy than BRAFi given alone, but also produce FEWER side effects in previous studies.

Thanks, ratties. - c