Maurie Markman, MD
The “right to try” is probably the most controversial issue in cancer medicine today. The concept that patients should be allowed greater access to experimental medicines has been transformed from a serious discussion about a remarkably complex and often personally gut-wrenching debate into what at times appears to be political grandstanding from commentators with limited understanding or appreciation of the potential benefits and risks to patients as well as the steps required to convert desire into reality.1
On March 21, the US House of Representatives passed a right-to-try bill that would allow terminally ill patients to receive investigational drugs that have been studied in phase I trials without applying through the FDA’s expanded access program.2
At press time, the Senate had not yet voted on the legislation.
It is important to acknowledge that this column reflects solely my opinions on the topic of right to try based on nearly 40 years of involvement in cancer care and clinical cancer research.
When I began my career in cancer drug development several decades ago, “early-phase” clinical trials were designed essentially to test an agent’s overall safety and to define an appropriate dose/schedule for possible future investigative efforts. In this era, objective responses in such studies were rarely observed, improvements in disease-specific symptoms were very uncommon, and any noted clinical benefit was quite short-lived. In fact, any focus on “symptoms” was related almost exclusively to adverse effects resulting from the anticancer agent. Some involved in drug development during this era described the selection of agents as “the drug-of-the-month club,” meaning there was limited justification to study a particular agent in a specific patient other than the simple and rather distressing fact it was that drug’s turn to be examined in the clinic.
Now fast-forward to 2001 and the landmark publication of the phase I trial of imatinib in chronic myeloid leukemia (CML). The selection of patients for this trial was based on the presence of a molecular biomarker hypothetically considered to be clinically relevant—a drug development process now known as precision cancer medicine.3
Of the 54 patients treated with imatinib at a daily dose of 300 mg or greater, 53 achieved a complete hematologic response. Of course, it is now well established that this class of agents has dramatically transformed the prognosis for individuals with CML.
Multiple other examples can be provided of an unequivocal clinical benefit associated with participation in early-phase clinical trials, justifying the conclusion that a patient’s desire to receive such therapy is neither irrational nor “false hope.” However, translating what is likely a common goal to provide patients with the opportunity to consider such therapies—the right-to-try concept—is extremely difficult today. Those who suggest otherwise almost certainly do not fully or even partially appreciate what is required to permit this to occur.
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