1. DiGiulio, Sarah

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One of the biggest challenges to making personalized cancer care a reality is understanding the potential of targeted drugs outside of their approved indications, says Richard L. Schilsky, MD, FASCO, Chief Medical Officer of the American Society of Clinical Oncology. In a telephone interview, he explained the key components of a new ASCO initiative to do just that.

RICHARD L. SCHILSKY,... - Click to enlarge in new windowRICHARD L. SCHILSKY, MD, FACP, FASCO. RICHARD L. SCHILSKY, MD, FACP, FASCO, Chief Medical Officer of the American Society of Clinical Oncology

"It's becoming more and more common to recommend molecular profiling-particularly for patients who have advanced cancer or patients who have exhausted all standard treatment options-to determine whether or not those results might suggest a course of therapy for the patient to try," he said.


"But many of those drugs would have to be used off-label, or would only be available in a clinical trial. The problem becomes-how does the patient get access to the drug? And, even if the doctor can get access to the drug and treat the patient, the rest of the medical community has no way of understanding whether that particular approach actually worked in that patient with those characteristics or not."


The program proposed by ASCO-and now currently being developed by a steering committee-would capture data from "real-world" clinical use of those drugs, and at the same time create incentives that would facilitate easier patient and physician access to those drugs.


"The point is to try to solve how to simplify access to the drug, and also how to learn from the experience of using the drug off-label so that ultimately we can gain more information about whether those approaches are worthwhile to pursue or not," Schilsky said.


He presented the idea at an American Cancer Society Cancer Action Network forum this spring (OT 6/25/14 issue), and he said ASCO plans to launch the program early next year. (The program has not been formally named but is being referred to as the national access program.) Schilsky also outlined the program in a recent Nature Reviews Clinical Oncology Perspectives article (2014;11:432-438).


He spoke to OT about how and why this initiative would lead to better cancer care.


1. How would the program work?

"The program would make drugs available to patients who are willing to enroll in a prospective observational registry study. The patients would need to be enrolled in a protocol that would be similar to a clinical trial-having both eligibility and exclusion criteria, though fairly liberal-and would need to consent to have their outcomes collected so that data could be incorporated into a registry.


"And, we hope to enlist the interest and support of a number of pharmaceutical companies who would be willing to make some of their marketed, targeted anticancer drugs available at little or no cost to patients through this program-similar to the way they might make drugs available for an expanded access program.


"The doctor treating the patient-if they believe that a molecular profiling test is medically appropriate-would have such a test performed (by whatever mechanism they would order such a test). And after reviewing results would determine whether or not one of the drugs that's available through this program is a good match for the molecular profile of the patient's tumor and might be a good treatment option. And we intend to include in the protocol some of the criteria that might be used to select a drug to use against a particular mutation site.


"The doctor would then submit the proposed treatment plan to an honest broker-an independent expert group who would review the clinical circumstances of the patient-review the molecular profiling test results, and review the proposed treatment plan offered by the physician to validate that it's a reasonable approach for this particular patient.


"Once validated, the drug would then be made available to the patient (at no cost to the patient), and the doctor would be obligated to capture the key patient outcomes, both toxicity and efficacy, in the registry."


2. And the benefits are...

"The basic premise is there are incentives for all the players to participate in a program like this one, which fundamentally provides a vehicle for capturing of good-quality, real-world observational data that we can all learn a lot from-that we are not currently able to learn from the off-label prescribing of these drugs.


"Over time we could imagine accumulating lots of data-from hundreds or thousands of patients-on the off-label use of targeted drugs under well-defined circumstances, where we know the characteristics of the patient, the results of the molecular profiling test, the specific treatment that's been given, and the outcomes for the patient. And then we would share that information broadly with all the participants in the program, and then over time broadly with all of the medical community.


"The patients benefit by having easier access to drugs that they are predicted to benefit from based on molecular profiling test results. The doctors benefit by getting easier access to these treatments. And ultimately the drug companies and the insurance companies benefit by learning a lot about the way in which these drugs are performing in these off-label indications-that information might influence their decision to develop a formal clinical trial, test a promising new lead, or potentially change direction-stop planning for a clinical trial that they were contemplating if it turns out that the real-world data does not support it."


3. What are the next steps to implement a system like this-and potential barriers?

"ASCO will organize the operational aspects of this, which we're writing a protocol for-and ASCO will ultimately keep the database for the registry. ASCO will also develop all the mechanisms for sharing the data. We're on a timeline to launch this program early next year.


"I've talked to representatives from all the stakeholder groups-doctors, insurance companies, patients, regulatory agencies-and everybody is intrigued by the concept here. Everybody sees its potential value; and essentially all the stakeholders have indicated a willingness to try to work toward making this a reality.


"I would say that the single biggest issue that's been raised is whether or not the data that would be collected in a project like this is actually of sufficient quality to be useful by all the stakeholders-that this real world observational data can actually enable a regulatory agency or a payer or even a clinical group to make decisions that they have to make-but we won't know that until the data comes in."