The Precision Medicine Misconception

Maurie Markman, MD

In the cancer research domain, the expression therapeutic misconception describes a situation in which patients mistakenly believe that the primary goal associated with their participation in a particular clinical trial is for the individual in question to attain clinical benefit. Rather, some academics and ethicists argue, the major intent of the strategy in actuality is to generate knowledge that may favorably impact the course of illness for future patients.

The aim of this commentary is not to debate the premise of this specific concept (with which this commentator strongly disagrees) but rather to highlight a different and potentially problematic therapeutic misconception now building within the oncology arena.

Amid the increasingly public discussion and often vigorous debate surrounding the general topic of precision cancer medicine, there appears to be a misconception—or one might even suggest a basic misunderstanding—of what the term is meant to imply. Some individuals seem to suggest that the term precision cancer medicine refers to a particular event or series of events whose occurrence would permit one to declare that, “The era of precision cancer medicine has arrived.”

Unfortunately, and quite similar to the profoundly flawed War on Cancer rhetoric, defining precision cancer medicine in this manner promises a biologically unattainable outcome—as in “August 17, 20xx was the day we were able to declare victory in our battle against cancer.”

When viewed in this manner, the limitations of where we are now and the flawed premise of the basic concept become clear, as medical oncologist Mikkael A. Sekeres noted recently in a commentary in The New York Times.¹ For how can one objectively suggest that precision cancer medicine will “cure” any cancer—or even substantially alter the course of most malignancies—in the relatively near future?

Surely, we must acknowledge that today there are a limited number of precision cancer medicine strategies that can be described as “a home run” (eg, BRAF inhibitors in metastatic melanoma) and far fewer as a “grand slam” (eg, targeting bcr-abl fusion in chronic myeloid leukemia).

To view precision cancer medicine in this manner completely misses the point. Simply stated, precision cancer medicine is not an event or a series of events and it is certainly not a day on the calendar. Rather, precision cancer medicine is a process, a conceptually powerful way to consider the scientific development of therapeutics in both preclinical and clinical evaluation and the subsequent delivery of treatments to individual patients with cancer.

The fundamental goal of precision cancer medicine is to permit antineoplastic therapy to be more precise by targeting molecularly defined abnormalities within the cancer or demonstrated differences between a patient’s cancer versus her/his normal cellular population. For the individual patient, the successful outcome of employing the process of precision cancer medicine will be a greater probability that the delivery of a given treatment program will result in a favorable clinical result (eg, improvement in survival, time to disease progression, decease in symptoms, improved quality of life) and a corresponding reduced probability that such treatment will only lead to therapy-related side effects (and no clinical benefit), compared with current management paradigms employed in a particular setting.

This process will certainly continue to be a key component of all future antineoplastic drug discovery paradigms. For example, provocative preliminary data reveal the cancers of patients most likely to achieve clinical benefit from CTLA-4 blockade possess a high mutation load, suggesting it may be possible in the future to select a patient population more likely to achieve a favorable outcome, and less likely to experience treatment-related harm in the absence of a realistic opportunity to attain clinical benefit.²

Investigative efforts within the precision cancer medicine sphere proceed from laboratory investigative efforts or possibly observations in a related clinical setting to subsequently explore the relevance in an individual patient or group of patients. While such research will never guarantee a favorable outcome or that a new more targeted delivery strategy will become a standard of care, the search for even more precise approaches to cancer management will simply not stop.

For instance, who could say today whether early provocative data³ suggesting that measuring estrogen receptor availability following fulvestrant therapy in patients with metastatic breast cancer has a predictive value that could ultimately be incorporated into a standard of care? But if the initial experience is not confirmed in future larger studies, this unfortunate outcome does not in any manner negate the precision medicine strategy to optimize disease management.

In summary, the essential message of this commentary is to emphasize that the concept of precision cancer medicine relates to the critically important current and future process of both antineoplastic drug discovery and subsequent clinical validation rather than the ultimate success of a specific approach in improving clinical outcomes in a given clinical situation.

References

1. Sekeres MA. Trying to fool cancer. New York Times. March 29, 2015:SR7.
2. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma [published online November 19, 2014]. N Engl Med. 2014;371(23):2189-2199.
3. Van Kruchten M, de Vries EG, Glaudemans AW, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer [published online November 7, 2014]. Cancer Discov. 2015;5(1):72-81.