› Forums › Ocular Melanoma Community › Another ASCO Update
- This topic has 27 replies, 5 voices, and was last updated 8 years, 6 months ago by JoshF.
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- June 8, 2016 at 4:47 pm
ASCO is now over and I thought I could provide a few more updates. As mentioned in an earlier post, this year did not include any major breakthroughs for melanoma. Still, the news is positive.
Five years ago the median survival for Stage IV melanoma patients was 10-11 months. Data at this meeting showed that patients treated with the BRAF/MEK combination (either dabrafenib/trametinib or vemurafenib/cobimetinib) have a median survival of just under 3 years. Similar results are found with patients treated with the anti-PD1 drugs pembrolizumab or nivolimab. For both groups, a subset of patients live far beyond that.
The highest response rates are with patients receiving anti-PD1 and anti-CTLA4 (ipi/nivo). We don’t yet know what the median survival will be with these patients, but it will likely be longer. The issue is that many patients have to stop treatment because of side effects. A new study is looking at pembrolizumab plus ipi, but using ipi at a lower dose. The ipi/nivo combination uses ipi at 3mg of drug per kg of body weight. This new study is at 1 mg/kg. The results look comparable to what is seen at the higher dosage, but the side effects are lower. The data is still new but are promising.
The big question is whether to offer BRAF/MEK first or immunotherapy first. The answer, it seems, is that it depends. The researchers who have focused on immunotherapy push for using it first, but for some patients targeted therapy should be first. Many doctors use targeted therapy when the patient has a lot of tumor or rapidly growing disease. The idea is to use fast-acting targeted therapy to slow things down and then transition to immunotherapy. This may not be the best strategy, however. Patients who do best on targeted therapy have lower LDH and fewer metastases. A lot of work still needs to be done, but the field is beginning to understand how to evaluate patients so as to tailor care for their specific situation.
The clinical trials for immunotherapy generally excluded patients with uveal melanoma. I heard a presentation that looked at a small group uveal melanoma patients treated with anti-PD1 drugs. The results are not very promising, though include some indications that a sub-group of patients might do fairly well. Cutaneous melanoma has a very large number of mutations, more somatic mutations that any other cancer. Uveal melanoma, in contrast, has very few mutations. This may explain the challenge of having immunotherapy work in this area.
I met with a company that is developing an IDO inhibitor. Some tumors release IDO, which starves T-cells and prevents them from attacking the cancer cells. This drug blocks the function of IDO. The company is particularly interested in combining their IDO inhibitor with an anti-PD1 drug. This combination might give the higher response rates seen in ipi/nivo but without the side effects.
Another company is working specifically with patients whose tumor has an NRAS mutation. They have a MEK inhibitor that seems to be effective in this group, about 20% of the cutaneous melanoma population. Currently no targeted therapy is available for patients with NRAS mutated tumor, so this could be a good advance.
Finally, a lot of conversation is happening about “value” in cancer care. The driving factor is the cost of cancer drugs. Globally we are seeing countries that will not provide the newer drugs because they are expensive. This leads to a conversation of cost vs. benefit. This conversation is most often tied to the price and the quality life-years that the price provides. A number of agencies have developed what are called “value frameworks” with which to make that evaluation.
The problem with all of these frameworks is that the patient perspective is not considered, or at best is considered only marginally. People are not numbers, and the care of people cannot easily be priced out in terms of days and years. Value varies from patient to patient. I heard of a young person who wanted to be treated with ipi instead of an anti-PD1 drug because if ipi worked they would be taking 4 doses and then be done with treatment. Anti-PD1 would be ongoing infusion for months or years. Some people want to go through anything and everything if it will buy them a few more months. Maybe they want to see their daughter get married, their son go off to high school, or experience a few more months of retirement. Others are not willing to go through potential toxicities and prefer to simply live out the time they have left. The MRF and other groups are pushing to be sure the patient perspective is part of this conversation. We are recommending convening panels of patients to provide input as the value discussion happens and as the frameworks are developed.
My overall perception of the meeting is that we still have a lot of work to do, but progress is still taking place. The feeling among melanoma doctors and researchers is definitely positive. I commented on the fact that we didn’t have any big news this year and one person replied, “I think it may be 2018, but more big news is coming.”
Tim–MRF
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- June 8, 2016 at 8:40 pm
Tim-
Anything on til therapy? Genetically modified t-cells? This a feasible treatment in the future?
Josh
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- June 8, 2016 at 10:41 pm
Josh, I didn't see anything on the ASCO website for Melanoma but I have a link from March 2016 which features an article from Dr. Weber on the topic. http://global.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option
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- June 10, 2016 at 2:26 pm
Take a look at these links Josh on Tils and Car treatments. Dr. Patrick Hwu of M.D.Anderson and Dr.Carl June. https://www.youtube.com/watch?v=3hlGq-3F1uQ&list=PL9ZmHiMj3aQ91tuo4VKRpib6QksYs6_lU https://www.youtube.com/watch?v=yGzJzzGj5Jw If you go to the 11.30 mark of the next one Dr.Hwu talks about tils. Best Wishes!!!!Ed https://www.youtube.com/watch?v=p1-qqIRzT6U
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- June 10, 2016 at 2:26 pm
Take a look at these links Josh on Tils and Car treatments. Dr. Patrick Hwu of M.D.Anderson and Dr.Carl June. https://www.youtube.com/watch?v=3hlGq-3F1uQ&list=PL9ZmHiMj3aQ91tuo4VKRpib6QksYs6_lU https://www.youtube.com/watch?v=yGzJzzGj5Jw If you go to the 11.30 mark of the next one Dr.Hwu talks about tils. Best Wishes!!!!Ed https://www.youtube.com/watch?v=p1-qqIRzT6U
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- June 10, 2016 at 2:29 pm
Sorry the first one was Dr. Weber, here is the one with Dr. June. https://www.youtube.com/watch?v=1sA_oz_1P5E
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- June 10, 2016 at 2:29 pm
Sorry the first one was Dr. Weber, here is the one with Dr. June. https://www.youtube.com/watch?v=1sA_oz_1P5E
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- June 10, 2016 at 2:29 pm
Sorry the first one was Dr. Weber, here is the one with Dr. June. https://www.youtube.com/watch?v=1sA_oz_1P5E
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- June 10, 2016 at 2:26 pm
Take a look at these links Josh on Tils and Car treatments. Dr. Patrick Hwu of M.D.Anderson and Dr.Carl June. https://www.youtube.com/watch?v=3hlGq-3F1uQ&list=PL9ZmHiMj3aQ91tuo4VKRpib6QksYs6_lU https://www.youtube.com/watch?v=yGzJzzGj5Jw If you go to the 11.30 mark of the next one Dr.Hwu talks about tils. Best Wishes!!!!Ed https://www.youtube.com/watch?v=p1-qqIRzT6U
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- June 8, 2016 at 10:41 pm
Josh, I didn't see anything on the ASCO website for Melanoma but I have a link from March 2016 which features an article from Dr. Weber on the topic. http://global.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option
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- June 8, 2016 at 10:41 pm
Josh, I didn't see anything on the ASCO website for Melanoma but I have a link from March 2016 which features an article from Dr. Weber on the topic. http://global.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option
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- June 8, 2016 at 9:48 pm
Thanks for the update, Tim. I appreciate the discussion on the expense of these drugs. If it is true that half to a third of all people will develop cancer in their lifetime, and cancer treatment ranges from $100k-$250k per year per patient, there is no insurance company or single-payer system that could continue to exist making those payouts. I question the high price tag assigned by the manufacturers. Also, vials of these drugs are sold in large increments where much of the product is not used and thrown out. They could easily sell them in smaller increments resulting in less waste and less cost, but also less profit. The manufacturers will continue to charge outrageous prices so long as insurance companies continue to foot the bill without pushback. I suspect my brother was denied cancer treatment at Kaiser due to their internal cost/benefit calculation but there's no way for me to know for sure. I only know he was on no treatment for the final month of his life (his doctor was "working on it").
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- June 8, 2016 at 9:48 pm
Thanks for the update, Tim. I appreciate the discussion on the expense of these drugs. If it is true that half to a third of all people will develop cancer in their lifetime, and cancer treatment ranges from $100k-$250k per year per patient, there is no insurance company or single-payer system that could continue to exist making those payouts. I question the high price tag assigned by the manufacturers. Also, vials of these drugs are sold in large increments where much of the product is not used and thrown out. They could easily sell them in smaller increments resulting in less waste and less cost, but also less profit. The manufacturers will continue to charge outrageous prices so long as insurance companies continue to foot the bill without pushback. I suspect my brother was denied cancer treatment at Kaiser due to their internal cost/benefit calculation but there's no way for me to know for sure. I only know he was on no treatment for the final month of his life (his doctor was "working on it").
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- June 8, 2016 at 9:48 pm
Thanks for the update, Tim. I appreciate the discussion on the expense of these drugs. If it is true that half to a third of all people will develop cancer in their lifetime, and cancer treatment ranges from $100k-$250k per year per patient, there is no insurance company or single-payer system that could continue to exist making those payouts. I question the high price tag assigned by the manufacturers. Also, vials of these drugs are sold in large increments where much of the product is not used and thrown out. They could easily sell them in smaller increments resulting in less waste and less cost, but also less profit. The manufacturers will continue to charge outrageous prices so long as insurance companies continue to foot the bill without pushback. I suspect my brother was denied cancer treatment at Kaiser due to their internal cost/benefit calculation but there's no way for me to know for sure. I only know he was on no treatment for the final month of his life (his doctor was "working on it").
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- June 9, 2016 at 5:00 am
Thanks so much for the summary! Very helpful. My mom is about to start a trial with 2 meds.. anti-Pd1 and an IDO inhibitor. The Dr had also suggested combo therapy but she is very nervous about the side effecrs so it was nice to see it mentioned here as possibly in the future comparable.
Thanks so much!
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- June 9, 2016 at 5:00 am
Thanks so much for the summary! Very helpful. My mom is about to start a trial with 2 meds.. anti-Pd1 and an IDO inhibitor. The Dr had also suggested combo therapy but she is very nervous about the side effecrs so it was nice to see it mentioned here as possibly in the future comparable.
Thanks so much!
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- June 9, 2016 at 5:00 am
Thanks so much for the summary! Very helpful. My mom is about to start a trial with 2 meds.. anti-Pd1 and an IDO inhibitor. The Dr had also suggested combo therapy but she is very nervous about the side effecrs so it was nice to see it mentioned here as possibly in the future comparable.
Thanks so much!
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- June 9, 2016 at 8:56 pm
thank you for the overview!
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- June 9, 2016 at 8:56 pm
thank you for the overview!
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- June 9, 2016 at 8:56 pm
thank you for the overview!
Tagged: cutaneous melanoma, ocular melanoma
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