[dropcap]A[/dropcap] new multidisciplinary consortium of more than 20 experts and stakeholders has come together at Penn to address the promise and challenges of precision cancer medicine. Through multiple conference calls culminating in a conference in May 2017, the group will tackle the hard questions that precision medicine raises for patients, providers, and payers. This is the first in a series of posts on the consortium’s work.

First, let’s define what we mean by precision cancer medicine (a definition used by Dr. Doug Lowy, Acting NCI Director, in 2015):

Interventions to prevent, diagnose, or treat cancer, based on a molecular and/or mechanistic understanding of the causes, pathogenesis, and/or pathology of the disease. Where the individual characteristics of the patient are sufficiently distinct, interventions can be concentrated on those who will benefit, sparing expense and side effects for those who will not.

As commonly understood, precision cancer medicine aims to identify optimal treatment strategies by matching therapy to characteristics of the patient’s tumor and/or characteristics of the person. The potential to tailor treatments to individual patients, and even more importantly, to their individual tumors, is captured well in this animation from Penn’s Center for Personalized Diagnostics:

And there are some success stories, in which genomic information has led to dramatic improvements in targeted treatment: for example, the drug imatinib (Gleevec) for chronic myelogenous leukemia; the drug trastuzumab (Herceptin) for HER-2 positive breast cancer; and the drugs gefitinib (Iressa) and erlotinib (Tarceva), for lung cancer patients whose tumors are positive for certain EGFR mutations.

But as a recent NEJM article noted, the overall promise of precision medicine is as yet unfulfilled, and the entire approach has been criticized. Skeptics claim that intratumor heterogeneity, or the likelihood that molecular analysis of a tumor sample does not represent other parts of it, poses potential limits to the benefits of targeting a specific molecular pathway. Experts in the Penn group noted that precision medicine is expensive and complicated, and while it is becoming more prevalent, the evidence base to support its real utility and value is limited. “Biology is way more complicated than we appreciate,” a consortium member remarked. Let’s unpack some of these issues.

Lots of people are doing it, and it’s expensive. The percentage of patients who received targeted cancer therapies increased from 11% in 2001 to 42% in 2011, while the proportion of private insurance oncology payments for targeted therapies grew from 22% to 63%. Overall, expenditures on oncology drugs among private insurance plans increased from $3,349 to $5,187 PPPM (a 55% increase) from 2001 to 2011. This spending has most certainly increased in the last five years.

So far, the evidence doesn’t support the claims. The only randomized, controlled trial of the precision medicine approach, (SHIVA), compared a molecularly targeted strategy to standard care in more than 700 patients with a variety of tumors. The investigators found no significant differences in disease progression, progression-free survival, or death. Other prospective studies and single-group trials have been just as discouraging. As one consortium member noted, “comprehensive genomic profiling of the tumors of patients with advanced cancer doesn’t deliver as yet…40% [of patients] have something actionable; half of them can actually find a drug, and 5% have a response to treatment, and it’s typically transient.”

The value of precision cancer medicine must include prevention and screening. Consortium members noted that although the focus of precision cancer medicine has been in the therapeutic space, it also offers an opportunity to improve cancer prevention though risk assessment, screening, early intervention, modification of current therapy regimens, and assessing residual disease. For example, tumor testing of colorectal cancer patients can identify families with Lynch syndrome, who benefit from increased surveillance and risk-reducing surgery to prevent primary colorectal cancer.

Going forward, the consortium will address the economic viability and sustainability of precision cancer medicine, with this broad focus on prevention, diagnosis and treatment. It will review the costs and effectiveness, and propose a value framework. Finally, it will review existing policy and regulatory tools that can affect precision medicine, culminating in recommendations for both public and private stakeholders.

In precision cancer medicine, as consortium members noted, technology and marketing are way out in front of the science and the policy. Economic viability questions today may be very different five years from now, and may change when the science catches up. This new consortium is determined help policy keep pace, and perhaps even lead the way.

The Consortium is made possible through a philanthropic gift to the University of Pennsylvania by Donald R. Gant, Wharton ’52 and the Gant Family. It is led by LDI Senior Fellows Justin Bekelman and Steven Joffe. Other members of the Consortium and their backgrounds are here.