For health plans, the impetus for step therapy—and the integration of pharmacy benefit managers (PBMs) and treatment pathways into the care process—is to lower costs, improve quality of life, and ensure that patients receive the most preferred therapy.
Today, the step process is likely familiar to both providers and to patients with cancer. Once a diagnosis is made and a treatment plan created, prior authorization is often required by the patient’s health insurance plan to determine if the plan will cover the prescribed anticancer drug or treatment.
From the perspective of hospitals, health systems, practices, and pharmacy management, step therapy in oncology is problematic on several levels. One complicating factor is that different commercial insurance plans have different prior authorization requirements. To date, many of these payers have some type of step therapy policy in place.
From the patient perspective, step therapy (also known as “fail first” therapy) can have significant negative consequences, such as the debilitating side effects that can occur when a patient fails a therapy preferred by an insurer. Step therapy may also require a drug produced by a company that does not offer patient financial assistance for that drug, potentially resulting in financial toxicity, among other challenges, before the patient can access another therapy.
In oncology, we frequently see step therapy triggered when oral chemotherapies are prescribed. The prior authorization approval process to treat a patient with an oral anticancer agent often involves the oncology pharmacy or provider submitting pages of documentation supporting the use of a specific oral agent for a patient.
To satisfy an insurance plan’s step therapy policy, providers start patients on a therapy, which from the health plan or PBM’s view is less expensive. When this drug fails the patient, providers then move forward to the higher tier (next step), more expensive medication.
Changing Coverage Determinations
Until recently, step therapy for patients with cancer was not permitted in Medicare Advantage plans. That changed in August 2018, when the Centers for Medicare & Medicaid Services (CMS) announced a policy change and issued new guidance stating that Medicare Advantage plans may use step therapy for Part B drugs, effective January 1, 2019, as part of a patient-centered care coordination program. This change has raised significant concern among stakeholders in the oncology community.
In May 2019 CMS issued a final rule that expanded step therapy to Medicare Part B drugs, but specified that antineoplastics are still to be included among the “protected classes,” and that insurers could impose prior authorization and step therapy requirements on new patients only.
For the oncology community, increased use of step therapy brings concerns that this approach will delay patient access to treatment and may limit patient preference, particularly as it relates to the individual’s goals of care. In some cases, step therapy may not actually limit the total cost of care. For example, if a patient’s cancer progresses early, more scans will be needed, and the patient will likely need to move to a newer, more costly treatment.
In oncology, step therapy has most often been used for ancillary, supportive care medications to manage treatment side effects such as nausea, vomiting, and neutropenia. The potential impact of the wider use of step therapy in oncology has stirred significant discussion and concern. The treatment of chronic myeloid leukemia (CML) is one example. The first-line therapeutic imatinib used to treat CML is now available as multiple generic products. As a result, many payers want to see the generic version built into pathways or step edits as the preferred first therapy because it is less expensive. For some patients, however, use of the generic drug may actually lead to higher out -of-pocket costs because there is no patient assistance program available for the generic. in this instance, step therapy may work against the patient. As this example illustrates, there are some questions in the development of this policy or pathway in terms of who is going to be affected by these requirements.
As more oncolytics become available as generics, we will continue to see discussion on this issue. The potential for financial toxicity for patients with cancer is well recognized. With more cancers becoming chronic diseases and patients being treated over longer periods, having access to copay assistance and other forms of patient assistance will be important to afford and maintain adherence to therapies to realize improved outcomes and patient goals of care.
Case Study: When Innovation Outpaces Coverage Decisions
Another complexity for the oncology community is the accelerating pace of knowledge and innovation. Renal cell carcinoma (RCC) is a case in point. National Comprehensive Cancer Network (NCCN) guidelines for advanced RCC called for use of sunitinib as a preferred regimen in the first line. But in April 2019, the FDA approved pembrolizumab plus axitinib for the first-line treatment of patients with advanced RCC. In this instance, the regimen was not included in the guidelines immediately after approval, so step edits may have required that patients first try sunitinib until coverage determinations and/or the NCCN guidelines were updated.
Step therapy can create a triangular relationship between the patient, the prescriber, and the payer. In this scenario, step therapy may have required the patient to try sunitinib first, even though the phase 3 KEYNOTE-426 study showed a statistically significant improvement in overall survival with the combination over single agent sunitinib (HR=0.53; P <0.0001).
This same scenario of requiring sunitinib before combination pembrolizumab plus axitinib in metastatic RCC lends itself well to the increasingly challenging issue of sequencing of therapies. In advanced RCC, after treatment with nivolumab plus ipilimumab or after sunitinib, you may be asked to try pembrolizumab plus axitinib. In this scenario, the provider talks to the payer, who says the combination therapy will be denied because the phase 3 evidence at that time is only for first-line therapy; therefore, their step-wise evaluation precludes use of this therapy.
In this example, step therapy does reduce costs because the outcomes are unknown, and there may be discussion about off-label use as well. The use of another immunotherapy (pembrolizumab) after failure on first-line immunotherapy (nivolumab plus ipilimumab) is an area that will be receiving a lot of scrutiny as we move forward. This issue has already emerged in EGFR mutation positive non-small cell lung cancer (NSCLC), where most patients will become resistant to treatment with EGFR tyrosine kinase inhibitors, and second- and subsequent-line treatments include immunotherapy.
When we’re looking at molecularly targeted agents in patients with lung cancer, we may see further step edits develop in the context of certain types of mutations that also predicates specific treatments and required steps for treatments that may preclude later treatment with some IO-based regimens.
Watch Your Steps
Step edits have already been developed in a number of disease states, including oncology, but recent CMS policy changes and proposals appear to signal increased governmental attention to step therapy as a utilization and cost containment tool.
In the simplest terms, step therapy seeks to ensure one therapy is used before another. For all stakeholders to discuss which drug or therapy is better than another, we need real-world data with true cross comparisons. Real-world data is imperative because step therapy decisions are currently based on clinical trial data. To appropriately evaluate step therapy for newer therapies such as immuno-oncology, in addition to cost savings, we must consider the potential chilling effect of step requirements on innovation leading to future advances and therapies. How might step therapy affect second-line access to a single IO therapy demonstrating 9 percent to10 increase in outcomes, if the first-line regimen precludes that IO agent from being used later on?
______________________________________________
ACCC President Ali McBride, PharmD, MS, BCOP, is Clinical Coordinator, Hematology/Oncology, The University of Arizona Cancer Center, Department of Pharmacy
Understanding both the benefits to be had from offering BsAb therapy to its community and the scope of this undertaking, Vanderbilt-Ingram Cancer Center took a novel approach with its APP-led BsAb step-up dosing clinic, which won the program a 2026 ACCC Innovator Award.
