MPIP: Melanoma Patients Information Page

The MPIP is the oldest and largest community of people affected by melanoma hosted through the Melanoma Research Foundation. It is designed to provide support and information to caregivers, patients, family and friends. Once you have been touched by melanoma—either as a patient or as a family member or friend of a patient—you become part of a community. It is not a community anyone joins willingly. But if you must be part of this group, you will find no better place to find the tools you need in your journey with this cancer, and the friends who can make that journey more bearable.

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Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

 

J Clin Oncol. 2013 Jan 7;[Epub Ahead of Print], A Ribas, R Kefford, MA Marshall, et al

 

TAKE-HOME MESSAGE

Tremelimumab failed to offer an overall survival advantage as first-line treatment of metastatic melanoma, but its longer duration of response may prove beneficial in a subgroup of patients.

Ipilumumab (IPI), a monoclonal antibody that blocks the immunoinhibitory function of CTLA-4, causes a reaction akin to taking the foot off the brake of a car and allowing the immune system to move forward in immune recognition and attack of melanoma cells. Randomized phase III trials of IPI demonstrated a survival advantage and the agent is approved in advanced, metastatic melanoma. A similar antibody, tremelimumab (TREME) was investigated in a phase Iii trial against standard of care chemotherapy, and is reported by Ribas in the Journal of Clinical Oncology online. This study failed to achieve a statistically significant survival endpoint for the antibody although there was a trend favoring the biological.

What are we to make of this seemingly disparate results? In the TREME trial, some patients in the control arm crossed over to receive IPI when that became commercially available in the US, likely improving the outcome for the control group. TREME was fairly toxic, and it is possible that better toxicity management would have allowed more patients to stay on study, receive more therapy, and result in fewer toxic deaths and withdrawals for toxicity. Schedule difference and patient entry criteria could certainly have also played a role. This negative trial should not dampen the enthusiasm for immunotherapy of melanoma but reminds us how careful we must be in designing, enrolling and managing patients in a study evaluating an agent with novel mechanisms of action and toxicity.

SUMMARY
OncologySTAT Editorial Team

Tremelimumab, a cytotoxic T-lymphocyte–associated antigen 4–blocking monoclonal antibody, has induced durable objective tumor responses in a subgroup of patients with advanced melanoma in early phase I/II trials. Ribas and colleagues conducted a phase III study to compare this novel agent with standard-of-care chemotherapy.

At 114 sites in 24 countries, 655 patients with treatment-naïve, unresectable, stage IIIc or IV melanoma participated in this study; 95% had stage IV disease. They were randomly assigned to receive treatment with tremelimumab or standard-of-care chemotherapy (dacarbazine or temozolomide). Of the 328 patients assigned to treatment with tremelimumab, 40 completed treatment; of the 327 patients assigned to treatment with chemotherapy, 33 completed treatment (22 with dacarbazine and 11 with temozolomide).

Based on an intent-to-treat analysis, the median overall survival for patients treated with tremelimumab was 12.6 months (95% CI, 10.8–14.3), compared with 10.7 months for those treated with chemotherapy (95% CI, 9.4–12.0; HR, 0.88; P = .127). Survival rates at 2 and 3 years were 26.4% (95% CI, 22.0%–31.7%) and 20.7% (95% CI, 16.7%–25.6%), respectively, for patients on tremelimumab, vs 22.7% (95% CI, 18.5%–27.8%) and 17.0% (95% CI, 13.3%–21.7%), respectively, for patients on chemotherapy.

Based on investigator assessment, the objective response rates were similar in both study groups: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. In addition, there were no major differences between the treatments in terms of the rate of complete or partial response. Defined as the time from random assignment to disease progression or death for objective responders, the median response duration was significantly longer among tremelimumab responders than chemotherapy responders (35.8 months vs 13.7 months; P = .0011). The probability of progression-free survival at 6 months was similar in the two treatment arms as well.

The most common adverse events related to the use of tremelimumab were gastrointestinal events (eg, diarrhea), dermatologic events (eg, pruritus and rash), and fatigue. The only grade ≥ 3 events reported in at least 10% of patients were diarrhea (14%) in the tremelimumab arm and neutropenia (10%) in the chemotherapy arm. Patients treated with tremelimumab experienced more cases of rash than did those treated with chemotherapy. Although most patients who discontinued treatment in either group did so because of disease progression, 43 patients stopped taking tremelimumab and 10 patients stopped taking chemotherapy because of adverse events. Finally, 7 deaths in the tremelimumab group and 1 death in the chemotherapy group were considered to be related to treatment.

Based on their study results, Ribas and colleagues concluded that tremelimumab failed to demonstrate a statistically significant overall survival advantage over standard chemotherapy in the first-line treatment of patients with metastatic melanoma. The duration of response was significantly longer after tremelimumab treatment than chemotherapy, although the rate of objective tumor response was similar with both treatments. The investigators believe that the durable responses seen in this trial confirm that tremelimumab may ultimately be of benefit to a subgroup of these patients.

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Anonymous's picture
Replies 4
Last reply 1/24/2013 - 12:21am

BRAF Inhibition Is Associated With Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients With Metastatic Melanoma

 

Clin Cancer Res. 2013 Jan 10;[Epub Ahead of Print], DT Frederick, A Piris, AP Cogdill, ZA Cooper, et al

 

TAKE-HOME MESSAGE

In patients with metastatic melanoma treated with BRAF-targeted therapy, BRAF inhibition was associated with increased melanoma antigen expression, T-cell infiltrate, and T-cell cytotoxicity, along with decreased immunosuppressive cytokines, providing a more favorable tumor microenvironment.

 

SUMMARY
OncologySTAT Editorial Team

BRAF inhibitors have produced impressive response rates in patients with metastatic melanoma, but early relapse is common. Immunotherapy agents have also been successful, and there is preclinical evidence of synergy between the two therapeutic approaches. Frederick et al evaluated the immune response to BRAF inhibition, alone or combined with MEK inhibition, in patients with metastatic melanoma.

A total of 16 patients with metastatic melanoma containing BRAFV600E received a BRAF inhibitor (vemurafenib) alone or a BRAF inhibitor plus a MEK inhibitor (dabrafenib plus trametinib). Tumor biopsies were performed before treatment, after 10 to 14 days of treatment, and at the time of progression.

BRAF inhibition was associated with increased melanoma antigen expression, with increases of 4.9-, 16.4-, 13.3-, and 14.1-fold in MART, TYRP-1, TYRP-2, and GP100, respectively. Melanoma antigen expression did not differ in biopsies from patients receiving a BRAF inhibitor alone or combined BRAF/MEK inhibition, except for TYRP-2, which was higher in the combination treatment patients. BRAF inhibition was also associated with significant increases in CD8+ T-cell infiltrate.

BRAF inhibition had significant effects on the tumor microenvironment. Immunosuppressive cytokines IL-6 and IL-8 decreased with BRAF inhibition, whereas markers of T-cell cytotoxicity increased. Of interest, markers of T-cell exhaustion (TIM3 and PD1) were also significantly increased with BRAF inhibition, as was expression of the immunosuppressive ligand PDL1.

Patients who progressed on therapy showed an increase in melanoma antigen expression and CD8+ T-cell infiltrate at the time of progression. Of the patients who progressed on BRAF monotherapy, 1 later received combined BRAF/MEK inhibitors. Tumor biopsy after treatment showed restoration of melanoma antigen expression and CD8+ T-cell infiltrate.

The study supports the hypothesis that combined BRAF-targeted therapy and immunotherapy may improve responses in patients with metastatic melanoma. BRAF inhibition enhanced the tumor microenvironment by increasing melanoma antigen expression and markers of T-cell cytotoxicity, while decreasing expression of immunosuppressive cytokines.

The immune response to BRAF inhibition may be limited, however, due to the paradoxical increases in exhaustion markers on T cells and in PDL1 seen in the current study. Further, melanoma antigen expression and CD8+ T-cell infiltrate were suppressed at the time of progression, suggesting reactivation of the MAPK pathway.

These findings suggest that successful combination therapy may require use of pro-immune cytokines, such as IL-2, and immune checkpoint blockade with agents that target CTLA-4, PD1, or PDL1 to augment the immune response to BRAF inhibition. Studies combining BRAF-targeted therapy and immunotherapy are currently underway.

 

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This does not sound like good news.  But aren't people on this forum getting some good results with the braf inhibition?

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buckytom's picture
Replies 10
Last reply 1/28/2013 - 11:19pm

I was diagnosed with Melanoma on January 9, 2013. I found a swollen spot in my neck, surgeon thought it was a cyst, but when he went into to remove it realized it was a lymph node. 5 days later I was told it was Melanoma. I have since had a PET scan, no primary was found - only one other node lit up on the scan very close to the original node. I am currently scheduled for a dissection of the nodes in my neck on Monday, January 21.

After reading this board I am wondering if I am jumping into the surgery too quickly. I am met with a medical and surgical oncologist, although not ones in a Melanoma center of excellence instead at our local hospital. Anyone have any advice - my first thought was to go through surgery and then with full diagnosis/prognosis get a second opinion from Mayo before staring any other treatments.

Any help, assistance, guidance would be appreciated!

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I was diagnosed with Melanoma on January 9, 2013. I found a swollen spot in my neck, surgeon thought it was a cyst, but when he went into to remove it realized it was a lymph node. 5 days later I was told it was Melanoma. I have since had a PET scan, no primary was found - only one other node lit up on the scan very close to the original node. I am currently scheduled for a dissection of the nodes in my neck on Monday, January 21.

After reading this board I am wondering if I am jumping into the surgery too quickly. I am met with a medical and surgical oncologist, although not ones in a Melanoma center of excellence instead at our local hospital. Anyone have any advice - my first thought was to go through surgery and then with full diagnosis/prognosis get a second opinion from Mayo before staring any other treatments.

Any help, assistance, guidance would be appreciated!

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Snickers60's picture
Replies 14
Last reply 1/21/2013 - 12:22pm

Yes !!!!'! Yeah !!! Amen !!! Glory be ! Yippee !!!!
Just saw Dr. B and everything was great for "my wonderful Wayne " :-)))

Noooo melanoma in MRI of Brain or PET Scan and all
Blood work looked great !!!
Whew !!!!!!! Alright !!!! Exhale !!!!!

All praise to God we give !!!

Warrior Wayne and Nancy - dancing a JIG !!!! -)))
Dance with us ????? :-)))

Matt. 15:13 "Every plant that my Heavenly Father hath not planted shall be pulled up by the roots". "With God all things are possible" ! Keep the FAITH !

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Yes !!!!'! Yeah !!! Amen !!! Glory be ! Yippee !!!!
Just saw Dr. B and everything was great for "my wonderful Wayne " :-)))

Noooo melanoma in MRI of Brain or PET Scan and all
Blood work looked great !!!
Whew !!!!!!! Alright !!!! Exhale !!!!!

All praise to God we give !!!

Warrior Wayne and Nancy - dancing a JIG !!!! -)))
Dance with us ????? :-)))

Matt. 15:13 "Every plant that my Heavenly Father hath not planted shall be pulled up by the roots". "With God all things are possible" ! Keep the FAITH !

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NYKaren's picture
Replies 1
Last reply 1/18/2013 - 1:55pm
Replies by: awillett1991

As many of you know, I've been on Zel for about a month now with few side-effects...SCC removed from back of knee, lots of skin tags around my eyes, some joint pain & very slight neurapathy.  I do take Benfotaime(sp??) 500  mg/day,  so perhaps the neurapathy & fatigue would have been worse.

Anyway, past few days, my right elbow has been swollen and painful to even extend arm.  Celebrex (which I had been on for the slight-medium joint pain)  or Alleve alone didn't work, Dilaudid 4mg did absolutely nothing, so Onc. started me on 5 mg. pred/day.  Yesterday (first day)  I stupidly took 10 mg in the a.m. because I forgot the pills I had were 10 mg & didn't break in half plus 2 Alleve morning & night. (pred was and is only 5 mg. in the a.m.)

This morning I woke up depressed (no surprise there) and pain was finaly a little better, and I took the 5 mg. and 2 Alleve.  BTW, I am on nexium 40 mg 2x/day.  A little nauseous, which is a good thing because I've been eating like there's no tomorrow before the Pred.  No nausea on the Zel.

I did take much larger doses of Pred when I had colitis from ipi, then hydrocortosine when I had adrenal insufficiency from the Pred! 

SO, I am interested in hearing others' experiences/dosages w/Zel and Pred.  if it's not for public consumption but you're willing to share, please message me.

THANK YOU VERY MUCH!

Karen

Don't Stop Believing

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annballard's picture
Replies 1
Last reply 1/18/2013 - 1:34am
Replies by: Janner

Hi Everyone,

I'm a 3a since 5/09 an no recurrance to date, however I'm heading to the determatologist tomorrow because of a new black lesion on my chest. My initial melanoma was on my calf. 

Does anyone know if this would this change my stage if it was local only? 

Thanks, Ann

Everything is for the Good.

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BrianP's picture
Replies 4
Last reply 1/20/2013 - 2:21am
Replies by: JerryfromFauq, Tina D, Anonymous, aldakota22

Hello fellow Melanoma warriors,

I have received so much information and inspiration over the last year.  I wanted to share with my fellow warriors a portion of a note I recently sent to my family and friends,

"Like a lot of cancers there is a significant chance of recurrence so I won’t know if I truly won my battle with cancer until I’m holding my grandkids about 30 years from now.  That’s the tough thing with being a cancer survivor; it’s always in the back of your mind.  If you really think about it though none of us really know how much time we have left on this earth, it’s just more prominent for cancer survivors.  The silver lining in all this for me is the realization that if I am fortunate enough to hold my beautiful grandkids many years from now I know I will have been a better husband, father and hopefully friend to many of you.  I will have counted more blessings, admired more sunsets, taken more walks on the beach, prayed more, loved more, and stressed less.  Not a day goes by now that I don’t thank God for all the blessings in my life and I have to admit I didn’t do this before my cancer.  I hope all of you had a wonderful Christmas and I pray for you and your family for a HEALTHY New Year."

It's been a tough run for me the past year but I know others have had it much worse than I and some are still going through tough times.  I hope many of you also are experiencing a richer life or have the opportunity to experience a richer life in the future.  I just recently retired from the Marine Corps and there's a saying in the Corps as well as the other Military services that goes something along the lines that freedom has an even deeper value for those warriors who have put it on the line to defend it.  In a way I think it's the same for those who have fought and are still fighting for our lifes in this battle against melanoma.  We all gain a much greater appreciation for how precious life is.

Take care,

Brian

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jtheisen29's picture
Replies 2
Last reply 1/19/2013 - 6:47pm
Replies by: Tina D, JakeinNY

 

Hi Everyone, 

 

I don't normally post here but do try everytime my twin sister has her scans for all those melanoma warriors searching for other stories like I did so many times. My sister was diagnosed with stage 3b while 5 months pregnant. She opted to do the 1 month high dose interferon and then the 1 year low dose. Fast forward 3 and a half years she has a beautiful little boy and is fully enjoying life. She just got scan results and she continues to show no evidence of disease. This forum has been such a help when I was helping her after diagnosis and still continues to be while keeping updated on the current treatments that are available. God Bless you all!

 

Jessica 

Former caregiver to twin sister with stage 3b melanoma

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Erinmay22's picture
Replies 12
Last reply 2/18/2013 - 10:12am

 

I'm getting ready to start PD1 on Monday.  Had biopsy and new scans taken yesterday (still haven't heard how much my scans have changed in the last 4 weeks...).  
 
Curious to hear from folks that took Ipi and failed and then took pd1?  What type of results did you see?  I know I've read a number of different things...  
www.melanomaandthecity.blogspot.com "people will forget what you said, people will forget what you did, but people will never forget how you made them feel' Maya Angelou

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Snickers60's picture
Replies 3
Last reply 1/18/2013 - 11:05am
Replies by: Tina D, aldakota22, NYKaren

Wayne had his Sedated Brain MRI and PET Scan this morning.    We see Dr. B. at 11 tomorrow morning.  

LITTLE SCANXIETY going on, :-)))  - ,but trusting God to have another good report waiting for us !    

LOTS of very sick people here this visit.    ALWAYS A WAKE UP CALL even when you are NED for a while.

Will update after we see Dr. B tomorrow.     Prayers are appreciated.   

Hope all of you are having a GOOD and TOLERABLE DAY and getting good reports EVERYWHERE !   :-)))

Nancy (devoted wife of 3 X Warrior Wayne) 

Matt. 15:13 "Every plant that my Heavenly Father hath not planted shall be pulled up by the roots". "With God all things are possible" ! Keep the FAITH !

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Marilynn Eiken's picture
Replies 1
Last reply 1/17/2013 - 8:02pm
Replies by: SStamps

I've written several times regarding my husband Tye.  Started with a mole on his back.  Mets straight to the brain and nowhere else back in Oct of 2011.  WBR and gamma knife followed.  Thought we were chugging along pretty good.  Started leukine last summer.  Then in November a small liver tumor which we irradicated with ablation therapy.  Then  in Dec the MRI showed enough change for the surgeon to say "I think its necrosis but its bigger and i think we should take care of it."  Low and behold.....melanoma grew back right where it seeded before.  Yesterday we actually got to see pictures of it.  We also got to see the "thin film" of black melanoma running along a vessel in the lepto menengies (sorry I know I spelled that wrong).  My husband follows no standard path.  Where there is LMD (leptomenengial disease)  there is usally widespread tumors.  He doesn't have any.  Where there is LMD there are usually symptoms.  He's very stable.  Some "maybe" symptoms but they can be explained through other pathways, ie-hearing has been very bad since surgery.  This happened last surgery and post WBR and hearing returned.  Abruptly after surgery, hearing TERRIBLE.  Has some  back pain.  Has always had some back pain and it doesn't feel different.  This melanoma is so sneaky and tricky. 

We are leaving next week to go to my son's Basic Military Training graduation from the Air Force.  When we return we will start ipi.  I feel its a good choice because we are shooting for long term effects and he has no real "measurable" disease which would be more Zel directed as he has a BRAF mutation.  Plus, it will be another stepping stone to the Anti PD 1 trials.  (Which I learned yesterday are coming to Mayo!)  I finally feel like our whole team of doctors is on the same page as we are.  Treat agressivley, goal is survival! 

I did some research on LMD last nite.   Not good.  A lot of my good warm fuzzies got lost in the literature.  One thing I have learned from this site is we are NOT statistics.  We are individuals and we have to hold on to that hope.  So Im hoping there are other lepto warriors out there that can share their insite with me.  I thought I found some mention from some of you so thought I'd put it out there again since the posts I found were from 2011.  We've got to beat this beast!

 

Marilynn

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mama1960's picture
Replies 6
Last reply 1/20/2013 - 3:29am
Replies by: JerryfromFauq, Tina D, mama1960, lou2, Anonymous

I have never been that person who goes to the doctor for checkups, but with all the Melanoma mess I decided to do the right thing. I had a blood test to check all the usual suspects, cholesterol etc. They are way out of the ball park and I am going to work on that. However, he also tested a couple of things I never heard of. They have to with inflammation and the possibility of heart disease. They are hs-CRP and Fibrinogen. The results are off the charts. High for the first one 2.9 and mine was 32.2. For the second one high is 464 amd mine is 658. He says this show a really large amount of inflammation somewhere in my body. Said it could be a result of cancer or the surgery, but there is no way to know for sure. Anyone out there familiar with this?

It is what it is.

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