PCOC16: Immuno‐Oncology Agents in a World of Precision Medicine

For decades, advances in cancer care have struggled with improving patient prognosis and extending survival by weeks or a few months at most, particularly in patients who may have developed an advanced form of the cancer. The advent of immunotherapy, however, has transformed this picture and has even raised the hope of being able to permanently cure these patients.

Patient-Centered Oncology Care^® (PCOC

At the 5th annual meeting of ^®), hosted by The American Journal of Managed Care (AJMC), November 17-18 in Baltimore, Maryland, Joseph Alvarnas, MD, associate professor in the Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope in Duarte, California, engaged experts with diverse experiences and backgrounds to discuss the contradiction presented by immuno-oncology agents in the world of precision medicine. Alvarnas is also the editor-in-chief of Evidence-Based Oncology, published by AJMC.

Joining Alvarnas were David Fabrizio, leader of Cancer Immunotherapy at Foundation Medicine, Inc; Sean Khozin, MD, MPH, senior medical officer at the FDA; and David L. Porter, MD, director of Bone Marrow Transplantation and Jodi Fisher Horowitz Professor in Leukemia Care Excellence at the University of Pennsylvania Health System in Philadelphia.

Alvarnas first asked Fabrizio to share his opinion on how a patient’s genomic information could best be exploited in treatments that utilize the immune system and the strategy that Foundation Medicine was working on to improve the efficiency of immunotherapy to develop a standard practice.

According to Fabrizio, using an assay score comes down to the human interpretation of a qualitative score, and it makes it hard to adopt to standard best practices, which leads to genomic solutions. “One such assay is the tumor mutation burden. We do this with [comprehensive genomic profiling, CGP] to understand the number of somatic mutations in a person’s cancer genome,” Fabrizio said. CGP, he added, gives an estimate of how the immune system will respond, and the company has been making strides with looking for more unified methods of analysis.

How can we bring standardization to the diagnostic industry?

“I think standardization is a huge part of the equation,” Khozin said. CGP, he believes, requires a substantially different approach, one that has not been typically available at large organizations, including the FDA. “Academic institutions have more data mining skills…what we need is a new approach to data science to develop predictive algorithms.” Khozin emphasized the important role of the “omics” approach—proteomics, genomics, the entire microbiome—in patient response to therapy.

Porter added that there have been efforts to integrate omics data in the clinic. “We are looking at biomarkers on T cells. A part of this is committing to and being able to have the right samples and tests,” Porter explained. “We are probably missing huge opportunities right now with our clinical trials; we are banking a lot of samples…DNA, RNA etc…but we don’t know how to manage them right now, although we will in the future.” He also added that trial design would change in the future, and that we may have to settle with smaller and more unique subsets of patients.

Khozin added that the FDA is looking into such trial designs, as well. “We don’t have to run a large study, rather leverage [electronic health record] data that is at the point of care.” The FDA has focused its attention on how care can be advanced, especially with immunotherapy increasingly being a part of the equation. The recently commissioned Oncology Center of Excellence (OCE) is working to consolidate oncology functions across the FDA to address the continuum of care in a coherent fashion, Khozin told the audience.

Paying for CGP and Immunotherapy

According to Fabrizio, payers have been slow to adopt to new genomic technologies, but that they are being more proactive and more engaging in discussions with their company. “I see this as an encouraging sign for the most efficient healthcare possible,” he added.

Porter also emphasized that the scale at which the chimeric antigen receptor (CAR) treatment is being developed, it ends up being very expensive. The treatment is being personalized for each individual patient, with strong biotechnology input.

“Third-party payers have not at all been involved in paying for this, although they have been asked to pay for the standard of care treatment,” he said. “Supportive care is not really being denied by payers, but academic institutions cannot fund this type of care…the biggest grants can maybe cover a couple patients a year.” Porter strongly believes that the pharmaceutical and biotechnology industry would have to provide maximal support for more clinical use of this technology. “We are breaking new ground here and we’d like to see more collaboration,” he added.

As of now, CAR treatment remains in the trial stage.

Can the FDA lend any support with helping payers navigate these novel technologies to develop payment policies?

“The FDA does not traditionally involve itself in cost mandates but we are thinking about value across the entire spectrum of drug development,” Khozin said, adding that Richard Pazdur, MD, who heads the OCE, is thinking of collaborating with the National Cancer Institute and CMS on value creation, not the cost of drugs.

When asked to provide a view of the direction that the field was moving toward, Fabrizio said that a more personalized approach for immunotherapy was necessary, such as using CGP to uncover neoantigenic epitopes. He added, however, that deciding on trial endpoints is a challenge, especially with a smaller batch of trial participants, which is the direction the field seems to be moving toward. “From a diagnostic test point of view, we want to understand actionable genomic targets, such as tumor mutation burden or identifying neoantigens.”

According to Porter, CAR-T is “a once and done therapy.” This raises the potential for alternate trial end points, such as response rate and achieving minimal residual disease status.

Khozin clarified that the FDA does not always push for overall survival. “We sometimes hear that sponsors say they have to do randomized studies for payers or other agencies…but we ask them not to conduct randomized clinical trials.” Referencing the cobas liquid biopsy companion diagnostic that was approved last year, Khozin said that the FDA has received several other proposals for such liquid biopsy tests, which points to using the levels of circulating tumor cells as a surrogate endpoint.

Porter summed the discussion by saying, “This era of immuno-oncology is revolutionary. It is one of the most exciting times in oncology, and the rate of change is staggering—from a clinical trial, regulatory, and data standpoint. Information is being generated at a very fast pace and needs rapid dissemination, and we need continuous conversation among the various entities to keep the progress going.”