It was not a matter of lack of efficacy but of a putative unfavorable risk-benefit ratio. The facts are that ixabepilone (Ixempra) was withdrawn by BMS based on a previous negative recommendation against marketing approval from EMEA (European Medicines Agency). I reviewed the EMEA CMPH (Committee for Medicinal Products for Human Use) negative opinion documentation of their decision which was based on the claim that the modest increase in survival did not outweigh the concerns over the medicine’s safety as to serious neuropathy, so that in their judgment the benefits of Ixempra in the treatment of breast cancer do not outweigh its risks.
This judgment is in error and their own reasoning provided is faulty: (1) although the benefit to overall survival (OS) was small, it is largely due to protocol and methodology constraints, while the benefit to PFS (progression-free survival) was clinically significant and indeed as I have pointed out, was the first and only such clinically significant survival benefit of any single agent tested in triple negative populations; (2) the reasoning re neuropathy is muddled and illogical, as there are dozens of other oncotherapy agents with grade 3/4 neuropathies, all approved by EMEA, and in a challenging-to-treat population such as advanced triple negative disease we require the fullest spectrum of potentially beneficial agents deployable serially through the various lines of therapy. In this case, the FDA did the more courageous and ethical thing and based on compelling survival outcome data, made another agent, as both monotherapy, and in combination with capecitabine (Xeloda), available to advanced disease patients. Indeed, I would argue that increasingly it is necessary to use PFS as a surrogate endpoint for overall survival.
Cancer Statistics Worldwide
The latest WHO show the lowest incidence of breast cancer in western countries is Greece and the lowest in Asian countries is Japan, and Greece and Japan are also the world's leaders in lowest incidence levels across all countries regardless of subgrouping. The USA. is 17th in terms of 26 countries compared, ranked from highest incidence to lowest.
As to 5-year relative survival, the picture is more complex, culled from multiple sources including the most reliable latest CONCORD and EUROCARE statistics along with WHO, NPCR, and SEER data: the best survival is in the USA, Canada, Sweden, and Australia in addition again to Greece and Japan; on the low end are East European nations, England, Ireland, and Wales, along with Brazil and Algeria. So in sum, the lessons are that just living in the USA is maximally favorable towards survival from breast cancer at the high end, largely a testimony to continued cumulative gains in quality of treatment; that in addition diet matters considerably in a positive direction in countries that lack the care resources of more advantaged countries, such as the benefit of the Cretan Mediterranean Diet in Greece compared to the relatively deprecated diet of countries like the USA, and in a negative direction for a country like the UK with a high end of resources and standards of cancer care but counteracted by singularly unwholesome diet.
The vast care resource advantage of the USA in turn helps to overcome, at least temporarily, the virtually epidemic level of metabolic syndrome including obesity and diabetes (in the USA, now one out of every two women are either overweight or clinically obese, one of the most frightening statistics ever recorded in health status in all modern time; within the near future mortality from metabolic syndrome (including obesity, insulin disorders, dyslipidemia, and possibly also hypertension) will be the number one killer exceeding that of all cancers combined. One saving grace: had the escalating velocity of oncotherapeutic breakthroughs been less advanced, the USA would be nowhere near the high end of the survival continuum.
The Dismal State of Health
In the background as a subtext is the decreasing level of physical activity and the rising level of alcohol consumption (in part due to continued mythology of some benefit from wines - there is none - and the never-die myth of "modest drinking") especially in increasingly younger women, coupled with what we call environmental bleed-through, like the increasing unhealthiness of health foods which have never been less healthy and where the vast majority include adverse high glycemic food content and sugars (the latter often disguised as "cane crystals", corn sweetener, evaporated or dehydrated cane juice, high fructose, fruit juice concentrate, to say nothing of plain old sucrose, glucose, dextrose, lactose, honey, maple syrup, and molasses, the "unhealth food" industry perpetuating the myth that there are real differences when in fact the scientific evidence indisputably shows that they are all equally deleterious junk). It is likely from the numbers we have re lifestyle factors that just more consistent physical activity coupled with caloric restriction and better diet (low glycemic, low sugars , high fiber, and with other components approximating the Cretan-Mediterranean Diet, etc., as I outlined in my CAM regimen) would provide a risk reduction benefit far vastly greater than every chemotherapy we have, to say nothing of adding optimal amounts of Vitamin D3 and reasonable avoidance of environmental pollutants.
In some sense, we are nearer than we think. Still, nice to know that treatment advances save.
Breast Cancer Watch