Payer Considerations for Molecular Testing In Metastatic Colorectal Cancer

Dr Haumschild aligns payer considerations with molecular testing and biomarker application for treatment of patients with mCRC.

Ryan Haumschild, PharmD, MS, MBA: There are considerations for molecular testing in metastatic colorectal cancer, and it’s continuing to grow. Our providers want to be thoughtful of: Are we screening patients at the right area? Are we doing it in house? Is it something we’re sending out? If we’re sending it out, what’s that turnaround time?

We consider molecular testing an important piece of that treatment journey. We know it’s important because it needs to be included in a lot of pathways and treatment order sets, and earlier identification of any genomic abnormalities gives us a target. With that target, we can leverage drug-specific medications that can focus on and provide better outcomes and better progression-free survival for a lot of those patients. We know that having specific biomarkers enables us to be best stewards of high-cost medications to ensure that each patient is getting the right medication for them. If a patient isn’t expressing a biomarker, we make sure we avoid that medication or don’t utilize it so we aren’t giving undue treatment to a patient.

Do the right tests matter? If we’re sending it externally or internally, does that matter? Does it matter based on the genetics? It does matter. Sometimes we can do it internally and it provides better turnaround times, and we can build that information into our electronic medical record. But externally, sometimes we can have more variability in panels and improve the number of tests we’re doing. It provides more of a comprehensive approach. But at the end of the day, testing matters because then we can more accurately predict response to therapies, leverage the unique targets, and reduce excess costs, so we can provide more consolidated approvals and not broad approvals. Because as a payer, I want to make sure the right patient is getting the right drug based on the right genomic [profile] and that we’re having good stratification of use specific to those targets. We can confirm that through molecular testing.

Key biomarkers are continuing to develop. One exciting thing about metastatic colorectal cancer is that we’re finding more targets as we continue to do more research. We’re starting to see these targets leveraged by the NCCN [National Comprehensive Cancer Network] within its guidelines as well. Now I think of the KRAS, NRAS, and BRAF mutations and even leveraging MSI [microsatellite instability]–high and dMMR [deficient mismatch repair] status. We’re also looking at tumor mutational burden if that’s available. Some of the other ones include the NTRK gene infusions.

One of the innovative ones that we’re seeing across metastatic colorectal cancer and gastrointestinal disease from the breast cancer area is HER2 [human epidermal growth factor receptor 2] amplification. How do we focus on HER2 amplification for targeting patients if only 3% to 5% recognize it? How do we create more targeted therapies for them? Lastly, when I think of emerging targets, more literature and more research is being done. That would be EGFR, PIK3CA, and MET amplification.

Biomarker testing is going to be essential to treatment decisions. We’ve seen this for solid tumor and hematology disease states. Why is it so important? We can screen that patient early on. We can recognize that they have an abnormality. If they do, we can target that, giving that patient their best chance at progression-free survival and overall response rate. It plays an important role in treatment decisions because not every medication is available for every patient, but now we have more of a streamlined approach. Almost like a prior authorization, if a patient comes back positive for expressing that genomic expression, then that’s a good thing for us. Because then we know and we can match the medication to that specific genomic abnormality and, that way, provide more of a streamlined approach and create a more consolidated use for patients who need it most. Because if I’m a payer or a health care provider, I don’t want to treat everyone with every single therapy. I want to know who’s most in need, who will respond the best to this therapy, and how we tailor that therapy to those patients.

Lastly, I want to focus on HER2 because it’s a great example. If someone has HER2 amplification, we know it’s present in about 3% to 5% of patients with metastatic colorectal cancer. HER2 positivity in a RAS or BRAF environment is associated with primary resistance and poor response to anti-EGFR therapy. Now we know what therapies the patients aren’t going to respond well to. How can we leverage the ones that target HER2 for a better overall outcome and progression-free survival and potentially overall survival?

When I look at the findings from the…study around genomic profiling and metastatic colorectal cancer that was published in 2019, some of the key points of the study focused on adherence to the guideline-recommended biomarker testing. That can be leveraged to reduce the exposure to expensive and ineffective therapies and also result in improved patient outcomes. If we’re leveraging the right biomarkers early on and we’re staying adherent to screen patients for these biomarkers, that means we aren’t spending a lot of money exposing many patients to therapies that they might not get benefit from. We’re providing the therapies to the patients, providing more of a tailored therapy, stewarding health care dollars, and most likely providing a better outcome for that patient.

When I look at some of the key points and takeaways, they assumed a conservative cost—around $6500—for a comprehensive next-generation sequencing panel. When you think about $6000 a week for something like cetuximab, if only about 4.6% of the undergenotyped patients received an appropriate therapy for 1 year, that would cover the cost of testing for all the patients in the study. In other words, when you steward therapy to patients who are most in need of it, it more than pays for the genomic tests. It saves the plan money, it saves the payer, and it better stewards health care dollars. At the end of the day, the patients who need it the most are getting the therapy, and we don’t have to expose patients to unnecessary therapies if they aren’t going to see that positive benefit.

Despite guideline recommendations and significant therapeutic implementation, overall biomarker testing rates in metastatic colorectal cancer remain suboptimal. There’s a huge opportunity for us to improve adherence, stay adherent to these guideline-recommended biomarkers, and make sure we’re screening them before treatment, reducing exposure of expensive medications to all patients and leveraging those unique therapies for those who need them the most. That’s ultimately what we’re trying to do as health care providers. Our payers and health care provider teams would appreciate that.

Something we’re always struggling with is the testing variability between health care providers to support patient care. You may see higher trends in the academic medical center integrated delivery network side. In community oncology, you might see different treatment trends and patterns. That’s difficult, especially as a payer or a patient. How can I know if I’m going to the right area where I’m going to get consistent proper care?

As a payer, 1 thing we need to focus on is leveraging some of our pathways and making sure we’re requiring some of this genomic testing before we give access to a medication. That sounds crazy, but it allows predictability of use across all environments, and it makes sure that someone doesn’t have access to a medication for a targeted therapy if they’ve never even screened the patient. It’s going to save the payer money, provide more effective therapy for the patients, and allow the provider to know the proper steps of when to screen. That’s where we’re headed. That creates shared decision-making around leveraging consensus panels like the NCCN and some of those biomarker best practices, and ultimately will provide more effective therapy at a reduced expense.

Transcripts edited for clarity.

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