News of a new weapon in the "War of Cancer" raged across the internet last week with the publication of a paper in the New England Journal on vemurafenib, an immune system-targeting drug used in cases of advanced melanoma. Heretofore, prognosis of patients with stage IV melanoma has been dismal, at best. Most die within 6-10 months. Various attempts over the past 15 years to improve survival with the likes of chemotherapy or immune-modulating drugs such as interferon have miserably failed to meet expectations. Paul Chapman's group at Sloan Kettering trumpets the fact that, at 6 months, 84% of participants using vemurafenib were alive compared to 64% who took the chemo agent dacarbazine.
This paper was presented at the American Society of Clinical Oncology and the resultant fanfare would have you believe Jonas Salk himself had announced a cure for the common cold. Here's a sampling of headlines from major media outlets covering the presentation:
'Time to Celebrate'; New Metastatic Melanoma Agent Wows ASCO
Drugs hailed as a 'major breakthrough' in treating deadly skin cancer
The Biggest Skin Cancer Breakthrough In 30 Years
Skin cancer 'wonder' drugs that could offer years more life in biggest breakthrough for 30 years
---Daily Mail (UK)
Pretty exhilarating, no? But let's take a look at the actual data. At six months, 84% of patients on vemurafenib were alive compared to 64% on the other standard chemo agent, dacarbazine. Based on this modest 6 month improval, the patients in the dacarbazine group were then switched over to vemurafenib for "ethical" reasons. So there is no data on longer term efficacy or median survival. Since the patients were switched, we'll never know if survival at 12 months, 18 months, or even two years is any different between the two drugs. Isn't that something that would be interesting to know? Furthermore, the results show that less than 50% of patients even responded to vemurafenib. And close to 40% of patients experienced toxic side effects incapacitiating enough to mandate dose modification or even outright temporary cessation of the vemurafenib.
The cost of the drug has not been released but a similar medication, Yervoy, retails for close to $120,000 for a one year course of treatment. Presumably, verumafenib will cost somewhere in this neighborhood.
Now I don't want to belittle the scientific achievement that vemurafenib represents. Being able to manipulate the expression of certain viral and neoplastic proteins at the genetic level is an exciting new frontier. But let's not confuse modest, incremental scientific advancement with real life efficacy. The headlines suggest a quantum leap in medical insight and intervention; which is misleading at best and perilously close to fraudulent misrepresentation at worst.
When it comes to late stage cancer, these pharmaceutical firms and the doctors doing the research have a major financial stake in promoting these newer drugs. Billions of dollars are in play. But this misleading propaganda campaign shamefully exploits a very vulnerable, desparate patient population....
Don't wanta sound like an A-hole, but if you can't recognize a malignancy on your skin, should you ...oh, never mind...
Its Evo-lution, in 5 billion years, we'll be a species that doesn't ride motorcycles, buy lottery tickets, or lay out in the sun...
and don't wanta get all Anthony Weiner here, but I've got this funny mole on my(Redacted), mind if I sent you a pic???
hope you have a BIG monitor,
This reminds me of the conversation about the metastatic prostate cancer treatment (sipuleucel-T?) that extends life for four months for a mere $93k. The last I read, CMS said they'd cover it. I don't have the answer to that ethical question, but it fits with the recurring theme in your blogs regarding the cost of end of life care.
The false hope from media coverage of new drugs is a shame. Family members call to see if their loved ones should take this new melanoma treatment, only to be disappointed. I had a patient this week say, "You guys must be celebrating, what with this new medicine that'll cure melanoma." The only thing we can take away from the clinical trials with ipilimumab and vemurafenib is that biologic therapy is much more promising than chemo for metastatic melanoma. Relatively speaking, there's been a lot of progress in the past few years.
Thanks for the interesting topics lately, Dr. Parks. There are still plenty of docs out here that share your 'romanticized' views on health care, yet find you to be quite 'patient-centered'. Keep it up.
Love this post, it brings to the front the re-occurring issues of quality of life vs quantity of life. My curiosity would be, if these patients were actually told that we could extend their life by 6 months but that would mean feeling sick as S*&^$ during the course of treatment would they still say yes to it? I see many of my patient who are palliative elect for different options when they hear the risk benefit analysis in non-medical terms. It makes me wonder what kind of care and quality we could give to terminal patients for the last six months of their life if we spent 93K on enhancing the quality of their last days instead of scrape together some extra days....Just sayin
Gil C Grimes, MD
Rural Family Doc Canada
btw the problem is not the docs at asco, they are just doing their jobs and they do it well.
its the industry driven press which pumps out its PR drivel.
im sure when the data is published in JCO or NEJM, they wont describe it as "he biggest breakthrough in 30 years" in the discussion section.
btw, interesting blog, i was linked here from a post in a forum im on...
tel aviv surg
Buckeye, several points:
1: Do you take any weight from lay-press articles? Thes are the same genuises that stated cell phones may cause cancer, based on the same level of evidence that states caffeine may cause cancer. Frankly, they are idiots whom couldn't get a story right if was written for them. Honestly, you are the one who appropriately rails on magie maher because she can't evaluate scientific papers.
2: Vemurafenib is NOT a immuno-modulatory drug rather a MAP kinase pathway BRAF kinase inhibitor in those patients with the BRAF V600 mutation (50% of metastatic melanoma patients). The immuno-modulatory drug is ipilimumab, a ant-CTLA4 antibody.
3: Both drugs HAVE been shown to increase overall survival which no drug has been shown to do in 30-40 years of trials.
4: You are correct on you 6 month OS numbers, however the response rate was 48.5% for the BRAF inhibitor vs 5% for dacarbazine. As a surgeon you likely don't know, but this is a huge response rate in metastatic melanoma. The only treatment which has had durable responses in the past is interferon in a highly select group of patients (around 5%). This is a very toxic treatment. Also, and independent data monitoring safety board met and determined the compelling evidence to allow cross-over, not a group in the pocket of pharma. Are you honestly saying we should NOT give patients this option to receive a medication that increases OS over a medication that does not? No medication up until these agents increase OS. I am sorry buckeye withholding medications in this fashion was stopped with the tuskegee experiments.
5: Did you actually read the vemuerafenib paper or the ipilimumab papers in the NEJM this month? Have you read last year's paper by Hodi in the NEJM? Actually this is a big step in the treatment of metastatic melanoma. Let me repeat this, NO DRUG UP UNTIL THESE TWO HAS BEEN SHOWN TO INCREASE OS...PERIOD. Added that there appears to be somewhere in the neigborhood over 20% OS with ipi and there is a kaplan-meier tail (stable survival rate), yes buckeye that IS a big deal. Granted we don't know where these numbers are going to go in the long term but using this as an example of a rant against big pharma frankly is shameful on your part. I am no fan of big pharma, certain academic docs association with big pharma, or the present drug costs. But honestly, the issue of cost and how we are going to pay for it needs to be held at the societal level. Do you see Obama having this discussion I don't. To be apolitical, George Bush had a huge chance to rein in drug costs with medicare D and allowing the govenment to act as one entity like the VA. Did he?...no. Very simply because pharma lobbyists paid off congress to make sure that idea went nowhere. Reform of the present lobbyist system is critical for any real change to occur.
In conclusion.....read the papers. Listen to the ASCO plenary session which had 2/5 abstracts based on the BRAF inhibitor and ipi your rant frankly came across as ignorant of the conclusions of the studies.
By the way buckeye the main grade III toxicities with the BRAF vemurafenib where squamous cell carcinoma that was treated with simple exicision. No cases of metatastatic disease. In reality this agent is not that toxic compared to other agents oncologists use. Ipilimumab is a different story, but like high dose interleukin (my mistake I think I said interferon above) the goal is a durable response.
response to above....
1)no question that the RR for plx is remarkable, but the OS rates are really a no brainer. dacarbazine might as well be a placebo...interesting editorial recently in nejm that questioned the ethics of a randomized trial between plx and dtic,
2)however the main problem is that the response is almost always limited to 6-9 months and they all recur, because the tumors are usually not really monoclonal but heterogenous. u succeed in eliminating the braf mutated population while the unmutated clone takes off and starts growing. even heard flaherty (mr plx) say this at the last sydney melanoma conference.
best bet will probably be combo pills which include braf but also other targets, to offset the heterogenity.but that will mean cooperation between competing drug companies...that would be interesting to say the least.
3) think u meant IL-2, not IFN, no?
(oh sorry u corrected that, sorry)
4) "As a surgeon you likely don't know, but this is a huge response rate in metastatic melanoma."
as a surgeon, i find that a bit condescending, n'est pas?...(ok, j/k) but even being a surgeon, i keep up with the melanoma literature...because i deal a lot with it.
tel aviv surg
I highlighted the media articles, not to delve into their scholarly merits (or lack therof), but rather for their propagandistic and sensationalistic effects.
In my post I acknowledged that the scientific aspects of the trials studying vemurafenib are worthy of discussion. (SEE 2nd to last paragraph in post). Incrementalism is the hallmark of scientific progress.
But let's be honest: the "wondrous" results leave much to be desired. You're right; we need to have a more honest, open discussion regarding the costs of these modestly more efficacious drugs and the relative burden society ought to be expected to bear. There's nothing shameful in pushing back a little bit against craven Big Pharm corporations that just LOVE to see outlandish headlines like what we saw for Verumafenib. 100 grand for a drug that extends life an extra 2 months 40% of the time is far more egregious of a sin(IMO) than a "rant" against Big Pharm by some random jackass in Cleveland.
Thanks for sharing this with us. It really hit home wiith me as I had a grand pa die not to long ago with this and I was not able to be there for him cause of my own heath issues
It was very hard but it helps to read up on it so I can understand it more!!
As an ONC pharmacist dealing on the back-end of some of these meds, just to clarify YERVOY runs 24K for the 20ml vial and we had a patient get a 40K dose (these numbers are at cost.)
Overall, great discussion.
Phenotypic traits and risk factors common in patients with endometrial cancer are obesity, menstrual disorders, a low fertility rate, late menopause, lack of ovulation and bleeding after menopausal. The risk is doubled in women taking tamoxifen to treat or prevent breast cancer. The maximum age of onset of endometrial carcinoma is the sixth and seventh decades of life.
This is very sad when the doctors and the pharmacies play with the life of the patients for their own benefit...it is medically and ethically wrong.
Having Stage IIIC metastatic melanoma that started from a small mole. It was not recognizable to me. It didn't look like much so I should what Mr. Drackman? Radiation starts in a week. After that I have to decide which drug treatment to use or just enjoy the time I have left. Thank you for the artical.
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