NEW YORK (GenomeWeb) – Moffitt Cancer Center is advancing a program to preemptively test patients scheduled to go on chemotherapy for pharmacogenetic markers that impair their ability to metabolize and respond well to nausea, vomiting, and pain medications.
Each year at Moffitt, around 10,000 patients receive chemotherapy, which commonly brings with it adverse symptoms such as throwing up and pain. Although patients are prescribed drugs to manage these reactions, some have genetic variants that make them poor metabolizers of these agents, making it likely they will continue to experience these ill effects. According to pharmacogenetics expert Howard McLeod, in an effort to optimize chemotherapy for cancer patients, Moffitt is planning to test them for four PGx markers immediately after their doctor determines they will need such treatment.
"We'll go in and get the genetic information in patients who are scheduled to have chemotherapy or have a diagnosis where chemotherapy is going to be the main option," McLeod, founding medical director of the Moffitt's Personalized Medicine Institute, told GenomeWeb. "The genetic information will be in place from the first dose of chemotherapy, [so] we'll be able to optimize the nausea, vomiting regimens and the pain control, and choose treatments more likely to work the first time."
More than 50 percent of patients on chemo experience nausea and vomiting despite receiving anti-emetic treatments, and these side effects can drive up medical costs an additional $4,000 per patient. Similarly, even when given analgesics, around 50 percent of cancer patients continue to experience pain due to chemotherapy or other treatments, the type of cancer they have, or comorbidities
As with other preemptive PGx testing efforts — at the University of Florida and Vanderbilt University, for example — the electronic medical record system will be the operational epicenter for Moffitt. The Tampa, Florida-based center has three different sites in the region where cancer patients are seen and a fourth site under construction. "The EMR is a critical part to this because it's physically impossible to be there prior to every patient receiving chemotherapy and whisper in the ear of the oncologist, 'don't forget to do this,'" McLeod said.
McLeod and others have been working with experts in charge of the EMR system at Moffitt to figure out the necessary adjustments so PGx data can be housed in the patients' records and doctors can be alerted if a patient has a marker that will make them unable to respond to treatment. "Another thing we've been working through, and certainly we don't have all the answers, is how do we convey the data to the patient so that they can take it with them to their other doctors?" he noted. "The electronic medical records are not very portable."
Moffitt uses Cerner's EMR system. "Even if the patient goes to a cardiologist who has Cerner [EMRs] it doesn't mean that the records can transfer easily," McLeod said. "So, we've been looking at old-school approaches like giving them a little card [with PGx results] that they can take with them."
For example, a handful of CYP450 enzymes are responsible for metabolizing 90 percent of prescribed meds. So, the variations that Moffitt will test cancer patients for could impact their ability to respond to a variety of drugs beyond anti-emetics and pain medications.
Even after applying the PGx markers currently known in the literature to be associated with metabolizing anti-vomiting and pain control meds, a proportion of patients will continue to respond poorly to these agents. Moffitt is planning to enroll these patients in clinical trials to try to identify the genetic markers associated with treatment response.
"We're going to build some cohorts of patients, in which we'll take the current state of knowledge, apply it, and we'll focus in on those patients who we still aren't helping … and do discovery work," McLeod explained.
Moffitt recently announced it would work with diagnostic shop Cancer Genetics to perform PGx testing for its patients and conduct a series of studies. In one of these studies, researchers will prospectively assess whether testing for certain genetic markers associated with metabolizing anti-emetic therapies can accurately predict which patients are at risk for experiencing chemo-induced nausea and vomiting.
In another study with Cancer Genetics, Moffitt will test cancer patients in the outpatient setting and identify genetic markers associated with pain. Variations in genes, such as OPRM1 or those in the CYP450 family, can hinder people's ability to respond to such drugs.
"For the discovery work, we'll do genome-wide association studies, to look more broadly across the genome for hits and then do more focused next-generation sequencing in the areas that seem to have some signal," McLeod said.
Moffitt readily sequences the tumors of its cancer patients for specific guideline-supported mutations to inform therapy selection. However, the center hasn't to date conducted PGx testing to inform management of treatment-related side effects in any "organized fashion," McLeod said. By partnering with Cancer Genetics, and in the future bringing in larger cancer institutions, Moffitt is hoping to develop a broader program around such testing.
In a statement announcing the Moffitt research collaboration, Cancer Genetics said it plans to incorporate clinically significant predictive markers discovered thorugh this effort into its PGx panels. The company further said it plans to launch a next-generation sequencing PGx panel later this year.
Moffitt is hoping other cancer centers will join this PGx effort so researchers can hunt for and validate predictive markers in larger patient cohorts. The data from research projects will be stored in a different repository than the EMR housing patient data from clinical PGx testing.
However, Moffitt is launching its clinical PGx effort as reimbursement for such testing continues to be uncertain. In recent years, labs performing PGx testing have complained of little or no payment from insurers. Thinking ahead about these challenges, McLeod said that Moffitt builds business cases for all of its projects, and the current PGx program is no exception. "At the least, there is internal clarity on the financial implications if we get no reimbursement and if we get all reimbursement," McLeod reflected. "We go into it with our eyes somewhat open."
Generally, according to McLeod, reimbursement has come through for PGx testing, when doctors are really specific about why testing is necessary. "It's not so much that we're making it clear that we're providing four results for the price of two," he said. "The insurance companies at some level care about that, but the folks we have to talk to get clearance for the payment … they want to know why we're using these four results." Average reimbursement for a four-marker panel is usually around several hundred dollars, he estimated.
However, insurers are being careful about reimbursing NGS panels used in tumor sequencing, acknowledged McLeod. Moffitt runs an internally developed "focused" panel that tests patients for specific driver mutations in genes included in treatment guidelines. Some of these markers involve, for example, BRAF in advanced melanoma, EGFR and ALK in non-small cell lung cancer, and KRAS in colorectal cancer. Then, for patients who are running out of options, Moffitt moves to another internally developed, but broader, panel to direct them to clinical trials or off-label drugs. If that doesn't work, then oncologists move on to Foundation Medicine's NGS tests for further guidance.
"When you use NGS testing for tumor sequencing, now you're getting into some big money," he said. "Then, the discussion becomes about what clinical decision is being changed. The drugs that are being influenced there often cost $100,000 per year, so it's a somewhat different discussion" than PGx testing for anti-vomiting and pain meds.