Wednesday, April 16, 2014

Clinical Trials and Patient Rights...An oxymoron????

A conversation about clinical trials has been ongoing on one of the forums.  Much of the discussion has been from voices frustrated with their inability to find out which drug they were actually given when they leave a trial so that they can plan their next step against their disease. Others seek lab results hidden from view.  And there are the voices of convention...saying..."Oh, you should ask more questions...apply for this or more carefully.  What did your papers really say?" Well, to that approach I say..."BULLOCKS!!!!"  The folks running these trials are fully CAPABLE of making themselves clear, in simple language, and providing answers to patients...IF THEY WANTED TO!!!!  I know some of you check both sites; I beg your indulgence.  But, I know many of you do not.'s what I DID say:

As many of you know, I have been a rattie in a clinical trial since Dec 2010. I started caring for patients when I was 19 years old. I have seen this world from all sides. It is complicated, often painful and un-pretty. Despite all I have seen and learned....I am thankful. Thankful to have had the honor to serve my patients all these years and lucky to have gained participation in my trial. Ipi wasn't even on the market when I started. I had no other options.

Which brings me to perhaps the most important point of this whole discussion. No one participates in a clinical trial for fun. Ratties are only there because they are running off a sinking ship. And the researchers? Many are wonderful, compassionate people who want to use their lives and careers to do good things for others. But, think about it. Where is their allegiance? It is to the drug company and their institution first. That is who is funding at least some of the research. The institution provides their paycheck. The drug company wants to do great wonders with the drug (read: make big bucks!$!$). And, if the researcher/institution wants to do more fab research...they've got to make the trial work so that they can get additional opportunities to participate in the next break-through trial. Next, they must have an allegiance to science. There is greater commitment to the results of the experiment, than to you, the individual. It is not really the patient's well being calling the shots. The participation forms are very clear on all of this. They say: You may do great. You may acquire any of PAGES of side effects. We (the doc, the institution, and the drug company) CANNOT be held accountable if you grow three heads, turn purple, or croak. Additionally, we will not be held financially responsible for any costs related to care for any side effects or extra head amputation that you may later need. And....if your scans or labs or wayward body doesn't play right, you will be dropped from the trial. Oh, can quit when you want, but...then you're done.

So, all this brings reams of papers and confusing medical terminology to patients in desperate circumstances. Signing up for a clinical trial is not for the faint of heart. Nor is the information presented in terms that most folks understand...especially when feeling sick, worn, and worried. Rather, patients feel they are completely at the mercy of the doc, the drug company, and the trial. They are afraid they are going to die. They are not going to quibble. In Chapter 3, from Cancer Clinical Robert Finn...he writes: "Cancer patients are in a one-down psychological position. They have to trust their doctor. They want a cure. They need a cure. They dare not risk any...alienation from the physician-researcher. So, they're very much inclined to do what the researcher wants and accede to the requests of the researchers."

I wrote my version here:

Bettin you are absolutely right. We need to make things consistent and better. There is no need for clinical trials to be so "random!" Yet, we ratties hope for good results for ourselves...and that even if we are not so lucky...then at least others will benefit from what is learned. WRONG again!!! In July of 2013, The Journal of Clinical Oncology published a review done of Phase II, III and IV cancer drug trials done between December 2007 and May 2010 and found that 50% of those results WERE NEVER PUBLISHED!!!!
My link:

Brian, my tumors were tested, because of the express desire from BMS, for PDL1 as well. The wording of the additional consent form was purposefully vague. Explanations from the researcher, clinical trial coordinator, and everyone else involved, ranged from..."Oh my hands are tied to give you more intel""I don't know nuthin bout birthin' babies!""Hmmmm." And trust me, honey. I'm a patient who asks! Most do not. I've made rounds with untold numbers of doctors. Some are very happy to escape the room as quickly as possible. But, others are perfectly willing to sit and really try to answer any question. Yet....more often than not...patients just nod and smile. But, when I return to the room after the doctor is gone, the questions flow. Sorry...just an aside. But, my expectations for getting the results of my testing??? Pretty much...NONE! Here's my rant:

When I see trials that are still comparing new meds to ineffective ones like interferon and dacarbazine, I feel physically ill. It is wrong. It is abusive. In a conversation reported from the European Cancer Congress in 2013, Ribas said, "taking all the studies...comparing ipi and dacarbazine vs dacarbazine, ...vemurafenib vs dacarbazine, dabrafenib vs dacarbazine, and trametinib vs dacarbazine - all of these studies have shown that another treatment was better than our old standard."

So what does all this mean and what can we do about it? It means that we still have a long way to go in attaining equal rights between drug companies, researchers, institutions and patients. I have no easy answers. All I can do is try to pay my fortunate circumstance forward, to make the path a little better, a little more comprehensible, for others. Some ratties squeak!!!

My best to you all. Celeste

Sunday, April 13, 2014

With melanoma: You can never be too rich or too thin! But, you can be too young!!!

Definitions to keep in mind:
Thickness (Breslow) - actual thickest part of a slice of the tumor...remembering that the lesion can rise above the level of your skin.
Clark level - a description of how deeply the tumor penetrated the layers of your skin.

Thin melanoma and late recurrences:  it is never too thin and never too late.  Richetta, et al.  Med Oncol.  April 2014.

"In the absence of risk factors, thin melanomas [generally defined as 1mm or less] present a long-term survival; however recurrences may occur....Median disease free survival of the entire cohort [in this study] was 26 months and three patients developed late metastases. Nine patients developed extra-nodal metastases as first recurrence, while cases of positive sentinel lymph node biopsy were not found....No consensus exists as to which patients with thin melanomas are at risk for metastases or late recurrences."

Sentinel node biopsy improves prognostic stratification in patients with thin melanomas and an additional risk factor.  Mitteldorf, et al. Ann Surg Oncol.  March 2014.

"Sentinel lymph node biopsy for patients with thin melanomas is not generally recognized as a clinical standard...931 patients had sentinel lymph node biopsies.  210 had thin melanomas.  Of the 210...All..showed at least one of the following risk factors:  ulceration (4%), Clark level IV (44%), nodular growth pattern (11%), mitoses (59%), regression (38%) or age </= 40 years (27%)."

....observed surprisingly high SLN positivity rate of 18%.  [Most of the literature says that for thin, 1mm or less, melanoma lesions the rate of finding a positive node is less than or equal to 5%.  Now, while that may sound nice....that is one of twenty people!!!]  "There was a trend towards a higher SLN positivity rate in younger patients. Breslow, ulceration, mitoses, nodular growth pattern, and sex did not reach significance.  Regression was significantly more frequently found in very thin melanomas (</=0.75mm) and tended to be significant in this subgroup."

"SLNB improves prognostic stratification in patients with thin melanomas having an additional risk factor....Our data suggest that SLNB should be offered to patients with thin melanomas, if ulceration, nodular growth pattern, mitoses or regression are present, or if the patient is younger than 40 years of age."

Identifying high risk patients with thin (</=1mm) primary cutaneous melanomas.  Gimotty et al. ASCO 2013. 

"The prognostic factors used to identify patients with thin melanomas at high risk of regional nodal metastasis or melanoma specific death include:  thicker tumors (>/= 0.75mm), deeper levels of invasion (Clark level IV or V), ulceration and dermal mitosis....Study cohort = 42, 080 patients with only one primary and no clinical evidence of metastasis at the time of diagnosis....Five year melanoma specific death rates were not uniform in 100 tumor thickness groups, but were stable in each of the following ranges:  4.3% - 0.01-0.17mm, 1.3% for 0.18-0.66mm, 3.1% for 0.65-1.00mm.  Among all patients, ulceration and level were the strongest prognostic factors.  Thickness was a weaker prognostic factor.  Four risk groups for regional nodal metastasis risk were identified:  
1) level IV/V (11.8%), 
2) level II/III with nodular or acral lentiginous histologies (15.1%),
3) level III and 0.11-0.17mm and not nodular or lentiginous (9.3%),
4) level III and 0.01-0.02mm and not nodular or letiginous (6%).
...Stratification schemes comparable to this will inform decision making."

My story:  Well, you can never be too rich if you are sick, in need of care longer than 2 minutes, or have to travel for your care!!!  Clearly, being thin (as applied to melanoma lesions) is not terribly protective.  I try not to say too much on the forums as Janner attempts to lull people out of their terror after having been diagnosed with an "atypical lesion"....she's definitely correct there.  No great risk, people.  It is gone.  Watch your skin.  Move on.  But, with this "thin melanoma" business...things can get murky!  Trust me!!!  My initial stats:  2003.  On right upper back.  Breslow measurement = 0.6mm.  Clark level IV.  No ulceration.  1/mitosis/hpf(high power field).  Yet, I had one positive node with "micrometastasis, Starz classification 1" (per Dr. Starz of Germany himself).  Later, we had a report from Martin Mimh, MD of Harvard, who noted that, yes, my tumor was a Clark Level IV (there had been some confusion on the part of the local 2-wong-fu pathologist) and "as you would expect" in such a case, I had a "positive node".  Age at diagnosis - 39.

As the thickness of the lesion was less than that indicated for a SNB at the time, we pushed for it anyway.  I am certain I would not be here today had I not had it done.  Turns out now, I WAS in a high risk group, despite the thinness of the lesion.  I was less than 40 years of age with a Clark level IV lesion. 

I don't want to frighten folks with this information.  But, this is the data.  And I am LIVING proof.
Take care of yourself.  Discuss with your melanoma specialist!  Yours, c

Friday, April 11, 2014

Happy thoughts!

See what angry, yellow T-cells can do to fat, ugly, pink blob cancer????  Go little T-cells!  GO! GO! GO!

Couldn't help but think of what Bentie might add when a nurse friend sent me this!!!  Pretty funny stuff!  Think of him and check the link below if you need a laugh....

B could probably add a few things... My life with a Nurse: A Man's Perspective

AND finally.....if life DOES give you lemons????

Make a Lemon Dress!!!

Much love and a happy Spring weekend to all! - c

Sunday, April 6, 2014

Background and latest info on anti-PD1 for melanoma

With the publicity of Merck's expanded access program (Hopefully they will actually TREAT a patient SOON!) for their anti-PD1 product, and the buzz around anti-PD1 generally...there have been many questions posed on the various forums about anti-PD1 lately.  Having had anti-PD1 (in the form of Nivolumab, BMS' product) as an ever present part of my world since December of 2010, I forget some folks don't know what it does and how.  I even looked back on my blog, and realized I hadn't posted many of the latest official results and you go:

What is anti-PD1?  In the simplest possible terms:  Anti-PD1 drugs are antibodies that block the switch on white cells so that they can now attack melanoma cells.  Specifically, programmed death ligand-1 [PD-L1] is produced by the surface of melanoma tumors.  That ligand binds to the infiltrating T-cells, down-regulating them.  Basically, turning those cells "OFF" to melanoma.  ANTI-PD1 blocks that potential interaction, so that the T-cells can now attack melanoma cells.

How is it given?  In your vein through an IV or port.

At what dose?  They are still checking the results of various doses: 1, 3, or 10mg/kg.  I was given 1mg/kg.  If I had to guess, the FDA approved dose will probably be 3.  Positive effects against melanoma have been seen at all dosage levels.

What are the side effects?  
Rashes and Fatigue - very common.
Arthralgias - joint pain is frequently reported.  Inflammation triggered by the immune response does not make joints happy.
Mucositis - irritation of the mucus membranes, from redness and tenderness to pain and lesions.  (The gut is just one long tube that starts in the mouth after all....see Colitis below.)
Hypothyroidism - not as common, but certainly has happened.  Often treatable with thyroid hormone in pill form, synthroid.
Colitis - irritation and inflammation in the bowel that can cause diarrhea and bleeding.  Sometimes, causing dehydration and the need for hospitalization, fluids, discontinuation of the drug for a time or permanently, and at times prednisone to stop the progression.  This is a fairly common cause of patients being taken off ipi and anti-PD1.
Pneumonitis - significant inflammation in the lungs that may be treated as noted above and has even been a cause of death for patients on ipi and anti-PD1, and obviously removal from a trial or treatment.
Pituitary failure and vision problems related to the optic nerve, as well as retinitis, have occurred but are not reported as common events.
Vitiligo - the depigmentation of the skin (and/or hair), leaving white patches.  Thought to occur because of the shared antigens located on melanoma cells and normal pigment cells.  It is considered a good prognostic sign that the drug is working against melanoma and occurs in 5-9% of patients on ipi or anti-PD1.

Survival, Durable Tumor Remission, and Long-Term Safety in Patients with Advanced Melanoma Receiving Nivolumab  Topalian, Sznol, Sosman, Hodi, et al.  Journal Of Clinical Oncology.  March 3, 2014

107 patients with "advanced melanoma [out of 306 patients with various cancer types], enrolled between 2008 and 2012, received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation."
In the 107 melanoma patients:  Median survival was 16.8 months.  1 year survival = 62%.  2 year survival = 43%.  In 33 patients with objective tumor regression, estimated median response duration was 2 years.  Toxicities in all 306 patients were similar to those previously reported. 
Conclusion:  Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations.  Responses were durable and persisted after drug discontinuation.  Long-term safety was acceptable. 

The above trial is the one that Dr. Weber was comparing the Moffitt trial results to on my last visit.  Link to the results we discussed:  discussion of my anti-PD1 trial results

The report below is from the sister arm, of NON-resected patients, from my anti-PD1 trial, though I am in the NED arm.  Also keep in mind, that when I started, folks who had been given ipi were not allowed in, but later arms were created that allowed patients who had failed ipi to participate.  Additionally, those of us originally enrolled in all arms were given vaccines, but since they were found to have no positive effect, later arms did not take them.  This report addresses all those arms EXCEPT mine, the NED cohort.

Safety, Efficacy, and Biomarkers of Nivolumab with Vaccine in Ipilimumab-Refractory or -Naive Melanoma.   Weber, et al.  Journal of Clinical Oncology.  December 1, 2013.

"We report the results of treatment of patients with unresectable metastatic melanoma who were ipilimumab naive (34 patients) or refractory (56 patients) and received nivolumab at 1, 3, or 10mg/kg.  Some patients also received an HLA-A 0201-restricted multipeptide vaccine."

"90 patients were enrolled at Moffitt Cancer Center between August 2010 and December 2012. 87 were evaluated for response, and three were too early for response evaluation. 74 patients had primary cutaneous melanoma. 8 had ocular mel. 8 had an unknown primary. 3 patients experienced progression on BRAF-i before enrollment.  10 had radiated brain mets. 5 patients in cohort 6 had untreated brain mets."

"Most common adverse event = fatigue. One patient experienced grade 3 bilateral optic neuritis, one had fevers, 2 others had pneumonitis...all resolved with steroids over 4 weeks to 4 months and discontinuation of treatment. Colitis was not seen in this trial.  Rashes were common, 1 required prednisone.  No treatment related deaths were observed."

"Median follow-up times were 20.3 months for patients in cohorts 1-3, 6.8 months for cohorts 4-6, and 8.1 months for all patients.  In ipi naive patients (n=34):  2 patients had a complete response, 6 had partial response, 7 had stable disease at 24 weeks, and 19 had progressive disease. Disease control rate = 45%.   In responders, median follow-up of 21.2 months, median duration of response was not reached.  In ipi refractory patients (n=53): 14 patients had partial response, 11 had stable disease at 24 weeks,  28 experienced progression.  Disease control rate = 47%.  In responders, median follow-up of 8.4 months, median duration of response was not reached.  For all 87 evaluable patients (ipi refractory and naive) the response rate was 25%, with a disease control rate of 46%.  Median duration of response was not reached at a median of 8.1 months.  PD-L1 tumor staining was associated with responses to Nivolumab, but negative staining did not rule out a response."

NOTE:  "12 of the 18 non-responders in cohorts 1-3 subsequently received ipi at 3mg/kg for a planned 4 doses. 2 patients had partial response.  2 had mixed response. 8 had progressive disease. 2 required steroids and infliximab for dose limiting colitis with ipi.  But, it demonstrates that patients who progress on Nivo can respond to ipi."

Hope that helps.  Wishing each of you my best. - c

Saturday, April 5, 2014

A life 'Les' Ordinary?????

After our last trip to Tampa and considering its hopeful implications....B said he hoped our lives would return to something a little more normal.  Well, of late...we have been in the normal repair business of life, especially after putting such things behind the back burner for the past couple of years.  I've already alluded to a new roof and septic tank repairs/draining...not that we personally did those things!  We finally had gutter guards installed so we no longer need hire the very strange folks who did that for us several years in a row, but whose work became so lackadaisical with ever increasing demolition of the surroundings that paying for the installation of the guards became cheaper!!!  Cracks in the wooden floor after a cold winter have been filled.  Baseboards and walls cracked by leaks BEFORE the roof repair have been mended and repainted...along with other baseboards and window sills.  Tubs recaulked.  Sink and tub drains replaced.  A leak in the plumbing upstairs was repaired with subsequent repair to the ceiling below it!!!  More painting. We tiled the area around and above our shower....yes, grouting became quite the adventure.  A new door and fixtures were installed in the shower....twice!!!  Areas under the dryer and washer have been cleaned with new hoses installed to the washer. {Sadly, just after the process, said washer is deceased with a new one to be delivered on Tuesday!!!} B has become quite the plumber!!! He ran a new line out to the back so that we can have a hose and faucet in a more convenient location.  All the unfinished pine furniture has been oiled.  The garage and 'playroom' have been cleaned with loads of flotsam carted off to Good Will and elsewhere. New work areas for my sewing and B's photography have been created. Curtains laundered. Clothes mended. Cars have been serviced. Drawers and cabinets cleaned. Roses and butterfly bushes pruned.!!!  Spring seems to be on the way! In fact, Mr. Sneaky Snake appeared in my living room yesterday, slithering around on the welcome mat!!! At first worried that he was a cooperhead...he turned out to be a much mistaken ringneck who was tossed out the front door by a very brave Bentie!!!   I fear many plants like my Nandinas, rosemary, lavender and other rather hardy herbs have given up after the sub zero temperatures we had this past winter!!  So, a revamping of the herb bed and some other areas may soon be in order!!!

To a life a bit more ordinary???!   HA!  Silly, Bentie!  YOU LIVE WITH ME!!!!- c

Skirts made and shirt repaired in "new" sewing area!

A beautiful rose and forsythia with a new purple blouse, al la recent sewing extravaganza!

Tile in process with art as inspiration!

Finished product! 

Table that B built.  Now this is how you watch Spring arrive!!  To a LIFE 'LES' ORDINARY!

Saturday, March 29, 2014

Ooh Child...uplifting sweetness from Nina Simone, The Five Stairsteps, and Steven!!!

Pick your preferred potion below, but I guarantee a gentle smile either way.  Yes, the road of life always has bumps, ridges, potholes, and even sinkholes!  Cars run off the rails, dreams shatter, pain shows up, and some days are lonelier than can be imagined.  There is an expiration date for all of us.  But, it's not today.  SO.....I'm going to use TODAY as best as I possibly can.  And since dear, sweet Steven was kind enough to send this bit of joy my way, I want to pay it forward and share it with you.

Ooh-oo child, Things are gonna get easier.  Ooh-oo child, Things'll get brighter. 
Some day, yeah.  We'll get it together and we'll get it all done.
Some day, when your head is much lighter.
Some day, yeah.  We'll walk in the rays of a beautiful sun.
Some day, when the world is much brighter.
Ooh-oo child, Things are gonna get easier.  Ooh-oo child, Things'll get brighter.

 Ooh Child - The Five Stairsteps

Ooh Child - Nina Simone

Wishing a brighter day for each of you.  Thanks, Steven. - c

Thursday, March 27, 2014

Anti-PDL1 for melanoma: A Phase 1 trial of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone 

The study above is now recruiting.  You can see all the details on by entering the NCT#.  Some folks on the forums are asking questions about it so I thought I could  try to answer a few points here.

Dabrafenib (Tafinlar) is a BRAF inhibitor that achieves a 70-80% response rate in melanoma patients with the BRAF v600E mutation.  Its down sides include the fact that the response can come with some nasty side effects and it can cease working for many melanoma patients in 6-9 months, though there are some out there who have done great for years. (You know you're the man Dick K!!!)  Trametinib (Mekinist) is a downstream inhibitor in the same pathway as the BRAF inhibitors.  The good news is that it seems to work in patients with NRAS mutations as well as those having the BRAF v600E mutation.  Recently the combo of these drugs was approved and is helping patients get rid of their tumors with fewer side effects and with less chance of melanoma learning how to work around the drugs.  (I have posts on Jan 13, 2013 and more recently on Feb 13, 2014 with more information on these drugs.)

MEDI4736 is an anti-PDL1 drug produced by MedImmune.  Anti-PDL1 is an antibody that blocks a switch on a melanoma cell that turns off your immune system.  Anti-PD1 drugs, are antibodies that block the switch on the white cells so that they can attack melanoma.

As someone who (along with most of the folks in my BMS anti-PD1 (Nivo) study at Moffitt) has had my tumor tested for the expression of PD-L1 on its surface...I have a very specific interest in the intel coming out about the anti-PDL1 drugs.   Back in 2012, The New England Journal of Medicine noted that in patients from a Nivo study, with a variety of tumor types, 25 of the 42 patients tested had tumors that were positive for PD-L1.  "Of these 25 patients, 9 had an objective response.  NONE of the 17 patients with PD-L1 NEGATIVE tumors had an objective response."  NOW...with that said....since then I have been told by the folks at Moffitt that that data was really important AND also told that it didn't mean so much after all.  We have still NOT been told what our personal tumors tested out to be...nor have I seen a report on that data.
To back up a step here is a basic info report on a different anti-PDL1 product:  Promising drug prevents cancer cells from shutting down immune system  
31 May 2013 19:19:03
"An investigational drug that targets the immune system’s ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. Updated data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Yale Cancer Center is one of the lead trial sites. The abstract was made public by ASCO in advance of the meeting.
The drug, known as MPDL3280A and manufactured by Roche Genentech, is designed to prevent a cancer cell’s mutated and overexpressed PD-L1 gene protein from putting the immune system to sleep. The overexpressed PD-L1 protein turns off the immune system’s T-cells by binding to its PD-1 and B7.1 proteins. In doing so, it disguises itself and evades detection and destruction by the body’s immune response.
This new drug is the latest advance in the burgeoning field of immunotherapy, which aims to boost the body’s immune system to fight the foreign pathogens of cancer. By blocking the cancer tumor’s PD-L1 protein, MPDL3280A frees the immune system to do its job. This PD-L1 targeted antibody was specially engineered to increase safety and efficacy over earlier immunotherapy agents.
Yale oncologists report that the efficacy of MPDL3280A was evaluated in 140 patients with locally advanced or metastatic solid tumors who had exhausted other means of therapy. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer, colorectal cancer, and gastric cancer. Yale oncologists say ongoing, durable responses were observed in nearly all patients who responded to the drug. Overall, 29 out of 140 patients (21 percent) experienced significant tumor shrinkage, and the highest number of responses were in patients with lung cancer and melanoma.
MPDL3280A was generally well tolerated, they say, with few immune-related adverse events. Some patients were continuing to respond more than a year after starting treatment.
“We have been very impressed by the response in seriously ill patients whose cancer had metastasized. So far, almost none of those who showed tumor shrinkage have gotten worse, which is extraordinary,” said lead author Roy Herbst, M.D., professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. “Immunotherapy treatment is providing new hope for cancer patients,” he added."
Currently there is a Phase 2 study ongoing, using anti-PDL1 with avastin in renal cell carcinoma.  There is also a Phase 3 study in progess using anti-PDL1 in patients with non-small cell lung cancer.  Neither of these studies have published outcomes thus my knowledge.
From ASCO, 2013:  A study of MPDL3280A (engineered anti-PDL1):  Activity, safety, and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma patients.  Sosman, Hamid, Lawrense, Flaherty, Hodi, et al.
"Melanoma tumor cells may utilize PD-L1 overexpression to escape immune surveillance...In Phase 1 study, metastatic melanoma patients received MPDL3280A IV every 3 weeks for up to 1 year and had tumor assessments every 6 weeks.  As of Feb 2013, 44...patients dosed at 0.1-20mg/kg were evaluated...61% received >/= 1 prior systemic regimen and 36% received prior immunotherapy.  14% of patients experienced grade 3/4 treatment related adverse events, including [elevated liver enzymes].  No grade 3-5 pneumonitis or colitis was reported. 38...patients...dosed at 1-20mg/kg prior to August 2012 were evaluable...An objective response rate of 32% (11/34) was observed in patients with cutaneous, mucosal or unknown primary histology (0/4 ocular patients responded).  Resection of remaining mass in a responding patient after 1 year of therapy showed no evidence of viable tumor.  Responses were durable, with 10/11 ongoing (responding patients on study for 3-10.5 months).  Analysis of archival tumor samples showed that PD-L1 positive patients had a higher rate of disease control versus PD-L1 negative patients [87% vs 20%]."
Clearly, as there is no data out on the combo this clinical trial is examining (to my knowledge) I don't have any intel to add that addresses that specifically.  But, for those of you with interest in the trial and its components....perhaps this background information will be helpful.
Wishing you all my best - c