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.

The information on the bulletin board is open and accessible to everyone. To add a new topic or to post a reply, you must be a registered user. Please note that you will be able to post both topics and replies anonymously even though you are logged in. All posts must abide by MRF posting policies.

Expand/ Collapse Topic
 
Replies By
View Topic
Research August 14, 2013
 

Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

 

J. Clin. Oncol. 2013 Aug 05;[EPub Ahead of Print], PA Ascierto, D Minor, A Ribas, C Lebbe, A O'Hagan, N Arya, M Guckert, D Schadendorf, RF Kefford, JJ Grob, O Hamid, R Amaravadi, E Simeone, T Wilhelm, KB Kim, GV Long, AM Martin, J Mazumdar, VL Goodman, U Trefzer

 

 
TAKE-HOME MESSAGE

Dabrafenib, a novel BRAF inhibitor analogous to vemurafenib, is shown to have clinical activity in this phase II single-arm trial of metastatic melanoma, with a response rate of 59% and progression-free survival of 6.3 months in patients with V600E mutations.

 

ABSTRACT

Purpose: Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. Our multicenter, single-arm, phase II study assessed the safety and clinical activity of dabrafenib in BRAFV600E/K mutation–positive metastatic melanoma (mut+ MM).

Patients and Methods: Histologically confirmed patients with stage IV BRAFV600E/K mut+ MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). The primary end point was investigator-assessed overall response rate in BRAFV600E mut+ MM patients. Secondary end points included progression-free survival (PFS) and overall survival (OS). Exploratory objectives included the comparison of BRAF mutation status between tumor-specific circulating cell-free DNA (cfDNA) and tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome.

Results: Seventy-six patients with BRAFV600E and 16 patients with BRAFV600K mut+ MM were enrolled onto the study. In the BRAFV600E group, 45 patients (59%) had a confirmed response (95% CI, 48.2 to 70.3), including five patients (7%) with complete responses. Two patients (13%) with BRAFV600K mut+ MM had a confirmed partial response (95% CI, 0 to 28.7). In the BRAFV600E and BRAFV600K groups, median PFS was 6.3 months and 4.5 months, and median OS was 13.1 months and 12.9 months, respectively. The most common AEs were arthralgia (33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 25 patients (27%) experienced a serious AE and nine patients (10%) had squamous cell carcinoma. Baseline cfDNA levels predicted response rate and PFS in BRAFV600E mut+ MM patients.

Conclusion: Dabrafenib was well tolerated and clinically active in patients with BRAFV600E/K mut+ MM. cfDNA may be a useful prognostic and response marker in future studies.

Journal of Clinical Oncology
Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma
J. Clin. Oncol. 2013 Aug 05;[EPub Ahead of Print], PA Ascierto, D Minor, A Ribas, C Lebbe, A O'Hagan, N Arya, M Guckert, D Schadendorf, RF Kefford, JJ Grob, O Hamid, R Amaravadi, E Simeone, T Wilhelm, KB Kim, GV Long, AM Martin, J Mazumdar, VL Goodman, U Trefzer

This abstract is available on the publisher's site.

Access this abstract now

Login or register to post replies.

Hello everyone,

 

I would really appreciate some help.My husband is in a very difficult situation because the illness is advancing too fast.

We have apply for the compassionate use of dabrafenib but is not coming until the end of the month.

At the moment we have only chemo.We are in Spain and my oncologist tells me this Braf inhibitors are still not commercialize in Europe.We would like at least to buy one month supply to give my husband the best fighting chance .Could anybody tell me where could i buy this pills urgently.I can fly anywhere.

tHANK YOU very much for your help!!

Login or register to post replies.

Hello everyone,

 

I would really appreciate some help.My husband is in a very difficult situation because the illness is advancing too fast.

We have apply for the compassionate use of dabrafenib but is not coming until the end of the month.

At the moment we have only chemo.We are in Spain and my oncologist tells me this Braf inhibitors are still not commercialize in Europe.We would like at least to buy one month supply to give my husband the best fighting chance .Could anybody tell me where could i buy this pills urgently.I can fly anywhere.

tHANK YOU very much for your help!!

 

Login or register to post replies.

Hello everyone,

 

I would really appreciate some help.My husband is in a very difficult situation because the illness is advancing too fast.

We have apply for the compassionate use of dabrafenib but is not coming until the end of the month.

At the moment we have only chemo.We are in Spain and my oncologist tells me this Braf inhibitors are still not commercialize in Europe.We would like at least to buy one month supply to give my husband the best fighting chance .Could anybody tell me where could i buy this pills urgently.I can fly anywhere.

tHANK YOU very much for your help!!

 

 

Login or register to post replies.

Hello everyone,

 

I would really appreciate some help.My husband is in a very difficult situation because the illness is advancing too fast.

We have apply for the compassionate use of dabrafenib but is not coming until the end of the month.

At the moment we have only chemo.We are in Spain and my oncologist tells me this Braf inhibitors are still not commercialize in Europe.We would like at least to buy one month supply to give my husband the best fighting chance .Could anybody tell me where could i buy this pills urgently.I can fly anywhere.

tHANK YOU very much for your help!!

 

 

 

Login or register to post replies.

Hello everyone,

 

I would really appreciate some help.My husband is in a very difficult situation because the illness is advancing too fast.

We have apply for the compassionate use of dabrafenib but is not coming until the end of the month.

At the moment we have only chemo.We are in Spain and my oncologist tells me this Braf inhibitors are still not commercialize in Europe.We would like at least to buy one month supply to give my husband the best fighting chance .Could anybody tell me where could i buy this pills urgently.I can fly anywhere.

tHANK YOU very much for your help!!

 

 

 

 

 

Login or register to post replies.

chalknpens's picture
Replies 4
Last reply 8/16/2013 - 11:58am

After much hesitation, I did go last week to have the Moh surgery on the squamous site on my chin. The little tiny spot required two Moh cuttings, and eventually a dozen sutures diagonally across the left front area of my chin. I had the sutures removed today, and will be seen again by the dermatologist in October. My jaw is now very bruised, and when asked at the post office by a friend, "What happened to you?" I told her that she ought to see the other guy. :-/

I am not perfect, but I am enough.

Login or register to post replies.

sbrooks90's picture
Replies 1
Last reply 8/16/2013 - 9:12am
Replies by: hbecker

Hello Everyone,

I am a 23 year old from Canada who has been dealing melanoma for 3 months now. I stumbled upon the board in the first few days following my initial diagnosis and will admit, I was scared to death to start reading these posts. You can see by looking at my profile all of the details but currently I am at Stage IIIa. There is so much information out there on the internet that tends to be misleading and this is honestly one of the best forms/support groups that I have stumbled upon. There are many people on here who are knowledgeable in this disease and willing to give great advice. So thank you to everyone in this group :) Although this is my first time posting... I have been following this group for a few months now.

Anyway just thought id share my thoughts.

Samuel

Login or register to post replies.

 

I have recently been questioned as to why I often say Oncoproteins and oncogenes. Genes and proteins are good and necessary. BRAF is a good and necessary part of our body makeup. We don't want to stop/remove the BRAF proteins and Genes from our bodies. We want to remove/block the Oncoproteins and oncogenes from their derogatory effects on our bodies.

What is BRAF?

BRAF, a member of the RAF family, is a protein kinase that is encoded by the BRAF gene. The RAF family of proteins includes 3 misinforms: ARAF, BRAF, and CRAF. While each isoform plays a role in the RAS-RAF pathway, BRAF is the main activator of MEK. BRAF plays an important role as an intermediary in the RAS-RAF signaling cascade, a pathway responsible for normal cell growth, differentiation, and survival.2

What is oncogenic BRAF?

Oncogenic BRAF can result from mutations in the BRAF gene. Various activating mutations (ie, somatic point mutations) in BRAF cause the protein to become overactive. This triggers a signaling cascade that can play a role in specific malignancies. Approximately 90% of known BRAF mutations are V600E mutations. These involve the substitution of glutamic acid (E) for valine (V) at position V600 of the protein chain, resulting in constitutively active BRAF. Other variants of this point mutation include lysine (K), aspartic acid (http://www.melanoma.org/node/add/forum/10D), and arginine (R). The V600 point mutation allows BRAF to signal independently of upstream cues.3,4,6,7 As a result of constitutively active BRAF, overactive downstream signaling via MEK and ERK leads to excessive cell proliferation and survival, independent of growth facors. Oncogenic BRAF signaling may lead to increased and uncontrolled cell proliferation and resistance to apoptosis (programmed cell death).

*********************************************
All these terms we tend to use and think of as bad, are bad when the go ONCO (I.E. mutate). we could not live witnhojut the good side of them.
I'm me, not a statistic. Praying to not be one for years yet.

Login or register to post replies.

 

Here is the home page that all should go to and go through the listings on the left and view the many write-ups and Videos contained in the articles. You will be amazed at what you will learn.

: http://www.biooncology.com/molecular-causes-

I'm me, not a statistic. Praying to not be one for years yet.

Login or register to post replies.

MattF's picture
Replies 8
Last reply 8/16/2013 - 12:22am

so about 6 weeks ago I noticed a largish (jumbo olive) sized lump under right ear, sticks out through the skin, hard, fixed...about 1 inch from primary stage 1 (maybe 2 unclear with shave biopsy) melanoma WLE that I had last Sep 2012

I saw onc and derm and both wanted biopsy

ultrasound was today...radiologist found it immediately and if=dentified it as a mass on or in my salivary gland.

he took 3 different pulls with Fine Needle.....sending it away for results.

anyone have any insite as to melanoma spreading to salivary gland?

kind of wild because it is litterally under my SNB scar from where they pulled 2 nodes and told me they were clear.

Login or register to post replies.

 

Hi, i just found this site today, as stated above, i have stage 4 Melanoma that has spread to my liver and upper GI track. The tumor on my GI track is causing blood to leak into the GI track, So yesterday i had the first dose of Yervoy and a blood transfusion . I see a lot of people on here have lots of bad side effects from the Yervoy, but what about the positive results from the Yervoy, Has anyone had good results ?????? Thanks, Jerre

Login or register to post replies.

aquamak's picture
Replies 4
Last reply 8/15/2013 - 7:27pm

It has been a long, stressful year since my original diagnosis in September 2012.  If you recall, a mole began to grow and change on my left neck.  After an inexperienced physician assistant at my local dermatologist told me it was a benign angioma and shaved it off, the pathology came back as invasive malignant melanoma (Breslow depth 1.5 mm at least, Clark level I, mitotic rate of 5 with no other “bad” characteristics).  I immediately went to Memorial Sloan Kettering Cancer Center and saw Dr. Steven Wang and on 10/18/2012, I had a WLE and SNB performed by Dr. Jay Boyle at Sloan.  Margins of WLE came back clear, final Breslow was 1.6 mm and a single Sentinel node removed, negative for melanoma.  Entire body PET scan and head CT clear also.  I was back to work a week after my surgery with no complications.  The second punch came on 10/29/2012 when Superstorm Sandy devastated the Jersey Shore and I began working the restoration efforts 7 days a week, 12-16 hours days at my employer, a local utility company.

During a much-deserved trip with my family right after Christmas, I noticed a lump right under my left ear above the scar from the WLE.  I saw the oncologic surgeon at Sloan on 1/6/2013 and he advised me that it was most likely nothing as I had told him I had a small infection at an ingrown hair in my scar.  Nevertheless, he had an ultrasound done right then and it came back as a slightly enlarged lymph node but nothing alarming.  He also performed a FNA, which came back benign.  I went on, assured it was nothing.  In April 2013, during a follow-up visit with the surgical oncologist, I told him the lump had not gone away and seemed to get larger.  He became more concerned and sent me for a full-body PET scan, which unfortunately came back showing 2 areas around the lump as suspicious for malignancy.  He then performed a very intense, painful FNA of the lump and scheduled me for a neck dissection and removal of my left parotid gland.  The day before the surgery in May 2013, the nurse called and told me the FNA biopsy came back benign.  I was still scheduled for surgery the next day however, they were first going to perform an excisional biopsy of the lump, do a frozen section and if nothing was found that was it for the time being.  If they found anything, they would perform the original surgery.  Unfortunately, I woke up after surgery with a drain and a scar from the top of my ear to the mid-line of my neck.  68 lymph nodes and surrounding tissue as well as my left parotid gland were removed.

The pathology came back 1 of 68 lymph nodes positive for melanoma plus 2 nodules of melanoma possibly infiltrating a nerve.  The perineural invasion later proved to be false after further testing but the nodules were considered in-transit metastasis.  This put me from a fairly “safe” stage 1B to a “serious” stage 3C in just 2 months considering when I first noticed the lump.  The doctors were somewhat baffled about the “elusiveness” of the recurrence and that the melanoma showed up as “spindle” cells considering my original site was primarily epitheloid cells. In addition, the pathology of the surrounding tissue showed the possibility that I may also have chronic lymphocytic leukemia (CLL).

So after additional visits to a leukemia specialist at Sloan, the CLL was ruled out but a pre-cancerous condition was considered however additional testing failed to prove that so a big sigh of relief on that front.

I was referred to Dr. Sandra D’Angelo at Sloan’s Melanoma unit for consideration into a clinical trail.  Two trials were offered, one for a Phase 2 trial of Dabrafenib as adjuvant treatment for Stage 3C melanoma patients with resected (removed) melanoma and the other for a Phase 1 trial of a dendritic cell vaccine against melanoma.  Unfortunately, I proved to be BRAF negative so the Dabrafenib trial was out.  I was very down about this but Dr. D’Angelo reassured me that Yervoy and the new PD-1 trials are better and more effective if I should have recurrence in the future and these are not BRAF dependent.

I was accepted into the dendritic cell vaccine trial and will have my stem cells collected on 9/11/2013 with my first of 5 vaccines to be given on 9/25/2013.  I chose to do the trail because frankly I feel like a sitting duck and live in fear of this disease every day.  I know that I will most likely have a recurrence but I want to give my self every chance to fight as I have a wife and 2 young children and I need to beat the beast.  I use the term “Mela-No-More” and live and hope by the words of Dr. Wolchuk from Sloan as he presented at the recent ASCO conference: “We have thrown the books out the window on melanoma and melanoma is no longer a death sentence.  It will become a chronic, manageable disease.”  I prayer every day for this and all afflicted by any cancer.

So, I wait for my 6-month PET scan in late-September and hope the trial provides some benefit to me.  My recent blood work all came back good with normal LDH levels and my full-body skin exam done today by Dr. Wang at Sloan was also good.

Please let me know if you have any suggestions for me going forward.

Mela-No-More

Login or register to post replies.

Commentary

Journal of Investigative Dermatology (2013) 133, 2133–2135; doi:10.1038/jid.2013.135

PUMA: A Puzzle Piece in Chloroquine’s Antimelanoma Activity

Ravi K Amaravadi1

1Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Correspondence: Ravi K. Amaravadi, Abramson Cancer Center, Department of Medicine, Perelman School of Medicine, 16 Penn Tower, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. E-mail: Ravi.amaravadi@uphs.upenn.edu

Top of page
Abstract

Chloroquine (CQ) can induce cell death in a subset of cancer cell lines, and some melanoma cell lines are quite susceptible. Although it is well known that CQ impairs lysosomal function and can serve as an autophagy inhibitor, the molecular target of CQ and the subsequent cascade of events that lead to cell death are not fully understood. Recent evidence indicates that in melanoma cell lines, CQ induces apoptosis by preventing degradation of the pro-apoptotic BH3-only protein p53-upregulated modulator of apoptosis. This finding adds to the unfolding story of CQ’s mechanism of action as a cancer therapeutic agent.

Login or register to post replies.

Pages