(iv)
(A) The rationale of Bristol’s (specifically Allison’s) strategy is to use monoclonal antibodies against CTLA-4 to mask it (CTLA-4) so that it can no longer serves as a brake to immunity. Sure--IF immunity is activated (which is not proven)--the immunity can attack many things, including one’s own normal cells, not just cancers.
(B) The notion to enhance immunity of a cancer patient started in 1890, as the report states, “Ever since the turn of the 20th century, when an American physician named William Coley treated cancer patients with a mix of bacteria to provoke an immune response to their malignant disease, there has been excitement over the idea of harnessing the immune system to fight cancer (see timeline).
(C) Coley’s experiment was NOT reproducible, not even by himself. This Fortune report neglected to tell the readers this.
(D) By 1980s when I was a graduate student at University of Illinois, scientists and physicians had abandoned immunotherapy against cancers, if only because cancerous cells (which basically are normal cells gone awry) do not have unique antigens on the surface that normal cells of the patient do not have.
(E) The mass media in US are full of hypes (at least in medical news), which have no basis in science. Top executives in most pharma companies are not scientists (neither the current chairman and CEO of Bristol are), nor are journalists. What they trumpets are foolish and endanger and cost patients, should the latter believe the bullshit.
(v) “In Allison’s case there was also frank disbelief that T cells even had built-in inhibitory signals, he says.”
It is untrue. “T suppressor cells” (a subset of T cells) was proposed, but in 1980s and 1990s (when I stopped paying attention to biology) immunologist can not find them or demonstrate this function.
(vi) Allison collaborated with a Princeton, NJ, company called Medarex [and they produced] "an antibody that could put the reins on human CTLA-4. They called it ipilimumab. A decade later, in 2009, the drug — later marketed under the name Yervoy — would belong to Bristol-Myers Squibb * * * [after] Bristol’s $2.4 billion purchase of Medarex * * * Jedd Wolchok, a cancer doctor and immunologist leading a Yervoy trial at Memorial Sloan Kettering [in Manhattan has a patient with melanoma that had metastasized] When the patient returned, he was almost free of disease. He’s still alive today, more than eight years later, with no sign of recurrence.”
(A) This kind of tales is not infrequent in melanoma patients. But how much of the improvement, even cure, can be attributed to ipilimumab?
(B) A review quantified the benefits:
Shah DJ and Dronca RS, Latest Advances in Chemotherapeutic, Targeted, and Immune Approaches in the Treatment of Metastatic Melanoma/ Mayo Clinic Proceedings, 89: 504-519 (2014; review)
www.mayoclinicproceedings.org/article/S0025-6196(14)00143-8/fulltext
(free to the public)
whose section IV A (headlined "CTLA-4 Inhibitors) is about Ipilimumab and Tremelimumab. In the former, it is said, “ Overall survival was significantly increased in patients receiving ipilimumab (ipilimumab vs glycoprotein 100 alone, 10.1 vs 6.4 months; HR, 0.66).”
HR stands for hazard ratio
en.wikipedia.org/wiki/Hazard_ratio
, NOT survival rate or improvement in patients’ quality of life. The review presented no statistics, specifically “p”
en.wikipedia.org/wiki/P-value
, to indicate whether the difference (10 and 6 months) was significant. (If trial size was small--enrolling few patients--the outcome might not be significant. The smaller the p, the better (or the more significant statistically between the new treatment and the old (or placebo)). In any event p should be less than 0.05. When p= 0.05, there is a chance out of twenty that the improvement of the new treatment is a pure coincidence --or falsely positive (ie, there is in fact no difference between the new and old treatments, though the new might LOOKS better). Most likely, p was less than 0.05 for ipilimumab, otherwise FDA would not have approved it, but the drug is insanely expensive, what is the cost benefit analysis?
Read on about Tremelimumab, which was deemed ineffectual but there was still two-month difference/advantage in survival rates: “(12.6 vs 10.7 months; P=.13) .” When p= 0.13, there is a chance out of eight that improvement of the new treatment is purely coincident. When p= 0.13, there is a chance out of eight that improvement of the new treatment is purely coincident; the chance is too high, and thus unacceptable.
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发表于 6-9-2014 17:02:15
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