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Personalized medicine for medicated persons
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When I reflect on a long medical career, I can identify series of major landmarks, some of which matter and others that don’t.
Somehow, it is important to me that Chester Meurant, BPharm, brought a small portable TV into our anatomy practicum class in 1969 and, while learning the basics of that science, we were able to watch Neil Armstrong on the moon as he took one small step for man and one giant leap for mankind. That set into context the ever-present balance between medicine, the frailty of life and the interactions with the cosmos.
Game changers
As a physician, I have participated in the introduction of cisplatin as a major lifesaving step into the management of metastatic germ cell tumors, with the PVB (cisplatin, vinblastine and bleomycin) and PEB (cisplatin, etoposide and bleomycin) regimens transforming a death rate of more than 70% into a cure rate of more than 70%.
I watched Tim McElwain, MD, and his colleague, Ray Powles, MD, struggling to overcome graft-versus-host disease at Royal Marsden Hospital while helping to introduce bone marrow transplantation into the United Kingdom as a potential game changer for patients with acute leukemia. This led to a refined technology that really saves lives for patients with a range of hematological disorders.
Learning from breast oncologists, Mark Soloway, MD, and I developed, in parallel, the paradigm of neoadjuvant chemotherapy for invasive bladder cancer, which increased cure rates by around 20% to 30%.
A few years later, I sat between George P. Canellos, MD, and Bruce A. Chabner, MD — two fine critical thinkers — at an ASCO Annual Meeting. We were impressed when Keith T. Flaherty, MD, presented startlingly long remissions in early-phase data from one of the first of the new game-changing treatments in melanoma management.
Thus, I have encountered a range of substantial and incremental changes that have really changed oncology practice.
‘Sea of progress’
Moving to the present, I greatly enjoyed — as I usually do — the recent contribution of Ian Tannock, MD, PhD, DSc, on personalized medicine published in The New England Journal of Medicine.
In this brief treatise, Tannock and John A. Hickman, DSc, noted the variability of molecular characteristics of individual tumors and the consequent heterogeneity of outcome of predictive and prognostic testing. They emphasized correctly that there is a paucity of data that show clearly defined gains in survival or its quality due to personalized cancer medicine.
This sensible stance reminds me greatly of the controversies surrounding the introduction of bone marrow transplantation in the early decades of its use, when zealots claimed its utility for all manner of disorders without structured trial data.
Marrow transplanters and some patient advocacy groups demanded the procedure for anyone who wanted it — for example, claiming that women with advanced breast cancer would be robbed of a chance at life by the withholding of this treatment prior to the definitive trials having been completed. What surprise they experienced when the definitive studies showed that bone marrow transplant was no panacea for breast cancer, might actually be harmful to these patients and had a very limited role for metastatic solid tumors.
Now we are on the crest of another wave in the sea of oncology progress. It seems to me there is no doubt that targeting of some genes will alter the fundamental paradigms of cancer therapeutics — namely, the melanoma work cited above — to the benefit of thousands of individuals and the community at large.
Although the costs of some of the new targeted therapeutic agents are prohibitive, we all know there is a difference between cost and price, and government always can become involved in creating approximation between those two entities — cost vs. price — if it has the stomach to overcome the contrarian lobbyists from the pharmaceutical industry. Our role as physicians is simply to focus on the introduction of true game-changing new approaches when possible.
This completes the circle of this essay: Is personalized cancer medicine a game changer?
I believe that Tannock and Hickman are on the right track. The answer is “yes” for some tumors and “no” for others, but the costs are prohibitive in both situations.
The price of molecular diagnostics — and of some targeted agents — is steadily falling, presumably because the companies already have met some of their costs, and competition is starting to influence the marketplace. This is a good thing.
I previously have expressed concern about the expectation by some of the corporations that work in this space that the health industry (payers, patients, hospitals, etc) should pay for their research and development work. In my view, the correct approach is that taken in yesteryear by those pharmaceutical companies that paid for research and development costs as part of a research budget, with free drug and reimbursement for tests that were not part of standard care.
I continue to regret the frequent expression of unvalidated hype by many of the corporate leaders, claiming greater success than actually exists, and sometimes extolled by government agencies and the media. We need to continue research in this domain, and I expect that it will lead to dramatic progress in the next decade.
It is quite reasonable that much of the hype around “moonshots” is focused on gene expression and mutation, and I anticipate that the molecular revolution will continue to shift the paradigms of effective medical care. However, we really must measure the parameters discussed by Tannock and Hickman and create studies that represent more than phenomenology and the smoking-gun hypothesis.
Recognizing the extent of tumor heterogeneity and the frequent disconnection between the molecular traits of primary and metastatic cancer, we must seek data that demonstrate which tumors actually have meaningful responses to treatments predicated on personalized medicine, how often these responses occur, at what cost — fiscal and physical — and whether these treatments are superior to the extant options.
Reference:
Tannock IF and Hickman JA. N Engl J Med. 2016;doi:10.1056/NEJMsb1607705.
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.