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The year of living dangerously
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The turmoil of December and early January has died down, and I have had time to think about the upcoming year, which seems to offer the possibility of being a year that could present some substantial hazards.
At a political level, one of the strangest U.S. presidential campaigns has been playing out in the press — hype and rhetoric seem to have dominated substantive discussion, and it is anyone’s guess as to which politicians will adopt specific policies on anything. Clearly outlandish statements command more airtime, and that tactic now seems to be commanding increased attention from several candidates.
Timely questions
In July 2014, in our opening editorial as Chief Medical Editors for HemOnc Today, John Sweetenham, MD, and I suggested it would be timely to ask politicians running for election a series of critically important questions, and I have summarized the most important below:
Absent a common-sense approach to military and political brinkmanship, an urgent response to global warming and a strategic plan to cost containment in health care — among other important issues — 2016 certainly could turn out to be a year of living dangerously for all of us.
As physicians have always played a prominent role in society, it seems to me it is time for us to question where our nation is going, and exercise the gifts we have as logical thinkers, intelligent members of the community and influencers of large numbers of our patients. I do not refer to partisan party politics as much as trying to identify statesmen and responsible politicians among the phalanx of candidates presenting themselves for political office, and using our influence to help their ascendency.
One of the very challenging issues in 2016 will be whether it is time for government to reconsider its directions to the FDA about the release of novel therapies into the marketplace. I spent several years in the past as a member of the FDA’s Oncologic Drugs Advisory Committee, and I was always impressed with the diligence of the FDA staff. They tried to evaluate reams of data dispassionately and honestly, and I believe their credo was to try to release useful drugs for use in the community. Gradually, as a result of a range of pressures from advocates and government, it seems the bar has lowered somewhat with regard to the true level of beneficial impact for our patients — the usual issue of statistical significance vs. clinical relevance.
Drug approvals
In 2014, the FDA released 41 new drugs into circulation, including nine anticancer agents. At the time, it seemed like a lot, but then I figured it was part of the new — and apparently very useful — wave of immunotherapeutics and targeted agents.
We saw another dramatic level of release in 2015, and this time, I am really not so sure. Clearly there are some very useful agents in both the above classes; having multiple iterations of immunoactive or targeted treatments ultimately will lead to refinement of therapy and reduction of costs, both of which are good for our patients and for our community.
However, close inspection of some of the released products causes me some heartburn.
We now have a new agent for second-line use in metastatic colorectal cancer that has increased median PFS from 5 months with placebo treatment up to a dizzying 7 months! The key phase 3 trial, which was well designed and well executed, reflected experience in 800 patients, one-third of whom were Japanese. I am not really sure why The New England Journal of Medicine took the paper as the differences in OS and PFS, although statistically significant, were clinically very small.
Similarly, the FDA approved another new agent that works sometimes for soft tissue sarcomas after initial therapy. This agent causes nausea, fatigue and diarrhea, infection, muscle breakdown and liver damage, but it was approved based on an improvement of PFS from 1.5 months to 4.2 months ... wow!
It is time for responsible government to review the rules that govern the FDA and its decision process. The staffers have no options and can only obey the rules.
For the future real welfare of our patients, the rules should require that the FDA evaluate the real impact of new agents and whether the population tested actually reflects the population in the United States (in the colorectal cancer study mentioned above, 30% of patients were Japanese and less than 4% were black).
They should consider the tough but important issue of where palliative care should be inserted into the treatment algorithm, as well as the impact of fiscal toxicity — which is so often attendant on these decisions — on the patient and family.
I wonder if any of the current political candidates (and/or their staffers) will be able to address issues as complex as these.
For more information:
Derek Raghavan, MD, PhD, FACP, FRACP, FASCO, is HemOnc Today’s Chief Medical Editor for Oncology. He also is president of Levine Cancer Institute at Carolinas HealthCare System. He can be reached at derek.raghavan@carolinashealthcare.org.
Disclosure: Raghavan reports no relevant financial disclosures.