In the Clinic

On Cancer: Memorial Sloan Kettering Researchers Report on Major Advances in the Treatment of Metastatic Eye and Skin Melanoma

By Media Staff  |  Monday, June 3, 2013
Pictured: Jedd Wolchok & Richard Carvajal Medical oncologists Jedd Wolchok and Richard Carvajal

Memorial Sloan Kettering clinician-researchers presented new research on treatments for two different types of melanoma this weekend as part of the 49th annual meeting of the American Society of Clinical Oncology (ASCO). The studies are shedding light on new therapies for advanced uveal melanoma, a rare cancer of the eye, and advanced skin melanoma – two cancers that have always been difficult to treat.

The first study showed that the experimental drug selumetinib is the first therapy able to improve progression-free survival and shrink tumors in patients with advanced uveal melanoma. If confirmed in another clinical trial, the findings might change the way this cancer has been treated for decades.

The second study, which was also published on June 2 in The New England Journal of Medicine, found that more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of the immunotherapy drug ipilimumab (YervoyTM) and the investigational antibody drug nivolumab, suggesting that these two drugs may work better together than on their own.

Targeted Drug for Uveal Melanoma

On Saturday, June 1, medical oncologist Richard Carvajal presented findings from a study testing the experimental drug selumetinib as a treatment for patients with metastatic uveal melanoma. This treatment more than doubled the time to progression when compared with chemotherapy. Many patients receiving selumetinib experienced tumor shrinkage, making selumetinib the first systemic therapy ever to benefit patients with this cancer. The findings are potentially practice changing for a disease that has previously had no known effective therapy.

In the Phase II trial, researchers randomly assigned 47 patients with metastatic uveal melanoma to receive selumetinib and 49 patients to receive the current standard therapy, temozolomide. In the selumetinib group, 50 percent of patients experienced tumor shrinkage, with 15 percent achieving major shrinkage.

In comparison, no patients in the temozolomide group achieved significant tumor shrinkage. However, patients whose disease worsened while on temozolomide were able to begin taking selumetinib.

In addition, selumetinib was shown to control tumor growth more than twice as long as temozolomide – for nearly 16 weeks versus seven weeks. Side effects caused by selumetinib were managed by modifying the dosage if needed.

“This is the first randomized study to show that a systemic therapy can provide significant benefit to advanced uveal melanoma patients, who have always had extremely limited treatment options,” says Dr. Carvajal, who is currently planning a confirmatory international, randomized trial for selumetinib led by Memorial Sloan Kettering.

“Confirming these results could form a foundation for new drug combinations that would maximize selumetinib’s effect, offering a whole new way to treat this historically untreatable disease,” he adds.

Although uveal melanoma is rare – there are only 2,500 cases diagnosed in the United States each year – about half of patients diagnosed eventually develop metastatic disease. The survival time for patients with advanced disease has held steady at nine months to a year for decades. There is currently no drug approved specifically for treatment of this cancer, which does not respond to the drugs given to patients with skin melanoma.

Dr. Carvajal and his team decided to test selumetinib because it blocks the activity of the MEK protein, a key component of a cellular process called the MAPK pathway. This pathway is activated by mutations in the genes Gnaq and Gna11 that occur in more than 85 percent of patients with uveal melanoma, inducing the growth and progression of tumors. Nearly 85 percent of the patients in the trial had such mutations.  

Combination of Immunotherapies for Advanced Melanoma

On Sunday, June 2, medical oncologist Jedd Wolchok presented data at ASCO that on the same day was published online in The New England Journal of Medicine. Results from this Phase I study showed that some patients with advanced melanoma of the skin might benefit from a combination treatment that includes the immunotherapy drug ipilimumab (YervoyTM) and the investigational antibody drug nivolumab. Patients who received this combination experienced dramatic tumor shrinkage.

“We pursued the ipilimumab and nivolumab combination because they each impact the immune system in a distinct but complementary way,” says Dr. Wolchok. “Ipilimumab activates a person’s immune system, prompting their T cells to begin attacking the tumor, while nivolumab further activates those T cells in a different manner, allowing them to continue the attack.”

Previous studies had shown that ipilimumab alone could prolong overall survival in advanced melanoma patients, and nivolumab alone could produce durable tumor responses in melanoma and other cancers. Combining the drugs was “quite logical,” Dr. Wolchok adds, and well supported by preclinical and clinical trial data.

Side effects from the drug combination were manageable. A multicenter, randomized phase III trial of the ipilimumab and nivolumab combination as a therapy for patients who are newly diagnosed with advanced melanoma is scheduled to begin in June 2013 and will be led by Dr. Wolchok.

“We are very excited about how well these two drugs work together. The major and complete response rates that these patients are experiencing are unprecedented for immunotherapy in advanced skin melanoma, and we are hopeful that this combination strategy will continue to be effective in the Phase III trial,” says Dr. Wolchok.

Read more about Dr. Wolchok’s study in stories appearing in The Wall Street Journal, New York Times, Reuters, Bloomberg, and watch a segment featuring Dr. Wolchok on NBC Nightly News.

Dr. Carvajal’s study was funded in part by an ASCO Career Development Award from the Conquer Cancer Foundation, the National Institutes of Health, Cycle for Survival, and the Fund for Ophthalmic Knowledge. Dr. Wolchok’s study was funded by Bristol-Myers Squibb Inc. and Ono Pharmaceutical Company Ltd.

Comments

I have been in the ipilumamab at the their ear center and recently was diagnosed with a pulmonary nodule positive for melanoma

I am Stage 4 malignant melanoma Reoccurred January 2013 in chest wall Originally diagnosed aug 2010. Did radical lymphectomy of neck and 1 year of interferon Currently on Zelboraf. Interested in new combination therapy. My daughter lives in Manhattan so I would have access to Sloan Kettering I currently live in Greenville SC They have a clinical trial unit here at the GHS health system Please respond

Terrell, to make an appointment with a Memorial Sloan-Kettering doctor, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

I submit my history to provide hope for all metastatic melanoma patients. My 1st melanoma was in 1986 (wide excision of left anterior chest). 18 mos. later it returned as a metastatic tumor in my left axilla which was excised along with 38 lymph nodes of which 15 had malignant melanomas. In 1989 a new primary melanoma was removed from the middle of my back. In Jan 1991 a 3x5 cm melanoma was confirmed in my chest below my left clavicle. I had 6 months of
experimental, high dose chemotherapy at U.C.S.D. Cancer Center followed by excision of the 50% smaller tumor which was followed by 21 days of high dose radiation therapy of the excision site. All of this was from Feb - Dec 1991. In 2007 a new primary melanoma was removed from my right upper back by Kaiser Permanente. Since the initial metastasis in July 1987, I have tried to eliminate all negative things in my life (processed foods, anything with preservatives, TV News, negative people) and replaced them with comedy, positive people and movies, healthy diet and regular exercise. I have also dropped two of the many doctors I have had that told me I had only so long to live. And last, but not least, I have asked for and received prayers from hundreds of friends, relatives and church members (many of whom did not even know me). I have at all times tried to focus on all the good things in my life and not the negatives, and I am grateful for every day that I am still here.

my husband has melanoma stage 4 .his doctors are not offering much interested to get the new therapy please.he had his first surgery in november 2012 and after radiation and interferon it's back

Hassina, if you would like to make an appointment with Memorial Sloan-Kettering, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thank you for your comment.

I was diagnosed with Stage 3 Melanoma over 1 year ago. I walked through the doors at Sloan Kettering and the rest is history. I have been operated on surgically by Dr. Coit and Dr. Ariyan. After 2 surgeries Dr. Dangelo reffered me to Dr. Wolchok and his team of geniuses after 2 golfball size tumors returned. I am currently in a trial with Immune Therapy drugs and the tumors have shrunk. A 3rd surgery was done to see the outcome. The doctors at Sloan are the best of the best and anyone who reads this post should be HERE is you are told you have cancer. THANK YOU SLOAN KETTERING!!!!

So nice to hear of the continuing progress of research from MSKCC, and of course Dr. Wolchok. He lead the transplant team in 2002, that performed my infusion.. Celebrating 11 yrs. August 14th.. God Bless to all the fine doctors and staff that work at this World Class Facility....

I was diagnosed with Stage 3 melanoma in March of 2008. I bounced around hospitals in Connecticut, and finally decided on MSK. We tried numerous trials at MSK and Yale (closer to my house) (Go Dr. Sznol !) before Dr Jedd Wolchok networked within the cancer community and found a trial at National Cancer Institute in Bethesda Maryland. Because of Dr Wolchok's networking he located my cure. He sent me to Bethesda with Stage IV melanoma, and 13 months later I'm 100 per cent cancer free. I consider Dr Wolchok my "Director of Second Chance at Life". He picked my winning medical lottery ticket.

My wife has Stage 4 malignant melanoma. Did 1 year of interferon, had two wonderful years afterwards, then diagnosed as Stage 4. Currently on Zelboraf (8 months). It seems that Zelobraf is not working anymore and we are interested in new combination therapy. We are from the EU and costs could be a major issue - can you provide us with any information about the costs? We have full medical insurance here, but are not sure how that works in the US. Thank you very much in advance for your reply! And to all those fighters against melanoma and their relatives - NEVER GIVE UP!

Andy, thank you for your comment. The staff at our international center will be able to help you with this question. You can find out contact information for international patients here: http://www.mskcc.org/cancer-care/international-patients.

Andy, we spoke to Dr. Wolchok, and he recommended you ask your doctor to check with Bristol-Myers Squibb and Merck about clinical trials. You can also go to clinicaltrials.gov to search for trials in your area. You will need to check with your doctor and insurance provider about cost, but ipilimumab (Yervoy) is approved for use in the EU. Thank you for your comment.

In 2004 I had surgery for Melanoma on my right lower leg. In 2008 it returned and I was diagnosed with Metastatic Melanoma. I gadually broke out with over 20 lesions all the way up my leg. My Doctor at City of Hope in Ca. sugested I see Dr. Brady at Sloan Kettering for Isolated Limb Infusion. A Dr. at Loma Linda told me an alternative was amputation. Needless to say I was terified. After sending Dr. Bady photos and copies of all my tests, she recommended I make the trip to NY. About a month later I saw her for a cosultation at MSK. There had been no new lessions breaking out and she told me that it looked like my own immune system was taking care of it and if it should return I would be a good candidate for ILI. It has since gone away completely. I am now 84 and it has been 5 years of remission. I would like to know what the chances of it returning are? I am Feeling very blessed.

Ellen, thank you for your comment. Unfortunately we cannot answer personal medical questions on this blog. If you or your referring physician wish to make an appointment at Memorial Sloan-Kettering, you may call 646-497-9072.

Dear MSK, thank you for our quick reply. We will consider Medical Records Review by Mail. Thanks to dr. Wolchok for his recommendation about ipilimumab. Our physitian however explained that given that my wife is stage IV 1mc (elevated LDH and several lessions), ipilimumab is not used in this cases. Is that true? Our clinical trail with vemurafenib officially ended today since one of the tumors (but only one) has progressed :( Any advice would be much apreciated. All the best, Andy

Andy, unfortunately we are not able to answer individual medical questions on our blog. We recommend you go through our International Center or speak to your wife's doctor. Thank you for your comment.

Is this trial open or closed.....Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye?? I heard one spot open, but may have been taken already?? Thanks.

Hi Ann, we consulted with Dr. Carvajal who informed us that the trial you mentioned is closed. However, we have three clinical trials for uveal melanoma that are currently open and more are planned to open in the fall. You can learn more at our clinical trials page:

http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=Carvajal&field_trial_diseases_value=All

Thank you for your comment.

My ex-husband was told by his primary care MD that he had a melanoma on his abdomen. The dermatologist won't be able to see him for a while.(rural area NY.)
I looked at the lesion being a nurse and it certainly looked like one. irregular scalloped black borders, black raised center, and various shades of dark brown,
About 9 mm I size. Do you have a dermatologist assoc. with your hosp. That could do a biopsy and make a definitive biopsy. His dermatologist can't see him in a timely fashion. Thank you.
Donna Leone
Figmentette@aol.com

Dear Donna, we do have dermatologic oncologists on staff who can expertly diagnose and
treat melanoma. We also have a number of locations in New York in addition
to our main campus in Manhattan. If your ex-husband would like to make an
appointment, please call our Physician Referral Service at 800-525-2225.

Thank you so much to all the Doctors and to the people who help to support Cancer Research, with out all of you there would be no hope, thank you again. I lost a daughter to Melanoma Skin Cancer in 2010, her name was Amanda Rose Miller and she is listed on the giving page with Memorial Sloan Kettering Cancer Center she was only twenty-four and full of life. I pray and hope that you all will find that cure someday, I read about all the great things you all are doing for people with this disease in finding that cure. Thank you again for everything and GOD BLESS all of you!

I was just diagnosised with choriodal melonoma. They will be treating with radiation. I am concerned about it spreading to my liver. I am having the tumor tested to see what type it is. Are there any trial I can participate in to slow progression if this has already spread?

Dear Sue, here is a listing of our clinical trials for melanoma: http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=&field_trial_diseases_value=Melanoma. If any of these look appropriate, the contact information is listed on the description page. You can also go to clinicaltrials.gov to search for trials in your area. If you'd to make an appointment with a Memorial Sloan-Kettering doctor, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for reaching out to us.

Hello. I am Florence and 6 years ago, I lost my 6 years old daughter from a neuroblastoma. I have a question for the researchers: since this cancer starts during pregnancy, is the mother exposed to the cancer cells from the fluids exchange. If yes, why doesn't it affect the mother too. Is it because her immune system proctects her? If yes, is there not a way to use that against neuroblastoma? Sorry this may be very ignorant from me to ask this but I just want to understand. Thank you in advance for your response. Florence

Florence, thank you for your comment. We are looking into your question and will get back to you as soon as we can.

Florence, we passed your question on to Dr. Cheung and this is is response:

Sorry to hear of your loss. Many neuroblastomas arise after birth. But even if the tumors begin in utero, mothers are never affected by them. We believe that the mother’s immune system fights them off. That’s why we are testing mothers’ white cells to see if they can help their children with neuroblastoma.

please help.. i am a 44 year old female with a pigmented line on my toenail i live in nj and have access to your basking ridge location .. i need a biopsey of the toenail who do you recamend i see? please let me know thank you for taking the time to read this..

Elizabeth, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. They will be able to answer your questions. Thanks for your comment.

when doing the biopsey of the toenail do i see a dermatologist or a surgical oncologist in your basking ridge location,

Elizabeth, the Physician Referral Service (800-525-2225) will be able to answer questions such as this.

Hi! I was diagnosed with "freckle" on my retina in 1994. From that point on I was under continuous care of Retina Specialists including Dr. Jose Martinez in Austin. In 2008 it grew and I flew to Boston for ProTon Beam Radiation Therapy by Dr. Evanglos Gragoudas. The procedure appeared to have stopped the growth.

In 2012 after undergoing yet another CT Scan of my liver, My oncologist, Dr. John Huber (Louisville KY) identified some lesions on my liver. In February 2013 I began an IL2 treatment in Nashville TN under the guidance of Dr. Igor Puzanov. I completed the treatments in February (Hospitalized five days - home for nine - hospitalized for another five days and off for two months). I did another series of treatments in May and again in August. However in August - I only completed 7 treatments then chose to stop treatment. It was just too hard emotionally, mentally, and physically. Let me add that I am a 53 year old patient who is physically active (walking and lifting weights for years).

Since I stopped treatment in August 2013 the CT Scans show that the tumors in my liver HAVE NOT grown - they are stable. I continue with the CT Scans every 6-8 weeks. My next scan is February 2014.

I'm not undergoing any treatment at the current time, as Dr. Huber believes the IL2 is still working in my body.

Should it grow I don't know what treatment option will be available or which we will choose. I PRAY everyday that there would be a cure for Ocular Melanoma. I pray for the doctor's making strides against this disease and I pray for the patients currently undergoing treatment.

I believe there will be a cure. Until then - be happy, be strong, be positive! Never give up!

Dawn, thank you for your inspiring words. Happy New Year!

Just want to add to the hopeful commentary of all who are being helped at MSK,
I thank God every day for the instruments of His healing, the staff of MSKCC!
It's been two years since my thyroidectomy and going strong, love to all my helpers! I add my prayers for a cure to those of Dawn and the other patients .
May God continue to bless us all! Amen!

Hello,
My 32 year old veteran wife was diagnosed with Ocular Melanoma in February 2013. March 2013, she had her eye removed due to the size of the tumor. September 2013, the cancer metalized to the liver. The tumor has grown huge; she is now under hospice care now as our doctors says there is not much they can do except keep her out of pain; which has been very difficult lately. My wife is very reluctant to try anything that is not holistic. Is there any hope for her? Any advancements? I appreciate any response,

Dear Gabe, we are so sorry to hear about your wife's diagnosis and all she's been through. We can't answer personal medical questions on the blog, but if you'd like to make an appointment with one of our specialists for a consultation, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

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