An Evidence-Based Argument Is Often the Fastest Route to Immunotherapy Authorization

Ezra Cohen, MD

Ezra Cohen, MD, prescribes immunotherapy (I/O) just about every day. He is a specialist in head and neck cancer, for which multiple I/O drugs have been approved. Usually, he said, getting payers to approve treatment is simple. But not always, and sometimes he needs to step in to make the case for his patient. That is especially true when it comes to off-label uses. “There are cancers I treat where I believe [I/O] could be effective but there is not an FDA approval,” said Cohen, codirector of the San Diego Center for Precision Immunotherapy and associate director of Translational Science at Moores Cancer Center at University of California, San Diego. “That’s where the challenges start to come in. We need to work at it.”

Other oncology practices face the same payment obstacles, and many are learning lessons about the importance of persistence, persuasion, and creativity in getting I/O drugs to the patients who need them (Figure). Nearly three-quarters (72%) of 110 respondents from oncology centers surveyed in 2018 reported that cost and payer approvals are the greatest barriers to offering I/O treatment.¹

Although patients often express a desire to be treated with I/O, the high relative cost of these agents as monotherapy and in combination can be a barrier. Also, these agents are administered for a prolonged period, which raises the financial bar. In the setting of unresectable melanoma, combination therapy of talimogene laherparepvec (T-VEC; Imlygic) plus ipilimumab (Yervoy) at $474,904 versus ipilimumab alone at $132,810 would result in an incremental cost of over $1.6 million for 1 additional patient to achieve an objective response, according to one study. Based on this, investigators concluded that “this amount may be beyond what payers typically are willing to pay,” although “this should not preclude treatment for individual patients for whom this regimen may be indicated.”²

Cost of I/O is a Universal Concern

“Everyone is concerned about the price of cancer drugs in general and specifically the price of [I/O] drugs, especially as they move into combination therapies,” said Lee S. Schwartzberg, MD, chair of the executive committee of the Association of Community Cancer Centers Immuno-Oncology Institute, which was established to help oncologists navigate the multiple challenges involved in providing patients with access to these drugs. Schwartzberg is also executive director of the West Cancer Center, Tennessee. Indeed, new oncology drugs in the United States are likely to have median annual prices around $200,000 per year by 2023, according to a January 2019 report from the IQVIA Institute for Human Data Science.³

In a recent statement for the IO Institute, Schwartzberg wrote that although I/O contributes comparatively high value in oncology, a viable framework for clear valuation of oncologic agents is still a need, and “this deficit remains a significant policy challenge, especially as current and planned proposals concerning reimbursement from a federal perspective, Medicare, and private payers are uncertain.” Schwartzberg added that policies that threaten to reduce margins on I/O payment could undermine the financial stability of community oncology practice.

For example, the Centers for Medicare & Medicaid Services has proposed narrowing the scope of coverage protections for drug classes that include antineoplastics. This would give payers more leverage to influence the costs of drugs and the number of agents available on formulary. This would also give payers freer rein to apply step therapy and tighten prior authorization requirements.

Given the clear advantage offered by some I/O drugs over prior therapies, insisting that oncologists work up to immunotherapies through step therapy programs would be putting the cart before the horse, said Melissa Dillmon, MD, chair-elect of the American Society of Clinical Oncology’s Government Relations Committee. “Step therapy policies are not appropriate in the field of oncology due to the individualized nature of modern cancer treatment, the lack of truly interchangeable clinical options, and thankfully the rapid development of newer and better therapies,” she said.

I/O Costs Will Drive Policy Decisions

Dillmon worries that the high cost of I/O drugs alone will become a determinant for policy decisions by payers. “With step therapy policies often encouraging the use of less expensive therapies first, new, costly [I/O] treatments, which are positively changing the future of patients with advanced cancer, may become a prime target for utilization management tactics,” she said.

Utilization management has already become an impediment to achieving the highest quality of care for patients with cancer, Dillmon contends. The time required for payers to process authorization requests affects promptness of care, and it's difficult to see the logic in requiring that patients fail on an inferior therapy first. “Such treatment delays can have a life-threatening impact for the patient whose cancer won’t wait,” she said.

For now, oncologists can employ certain tactics to improve their chances of gaining approvals for needed medications, oncologists interviewed for this article said. Payers more readily cover I/O therapies that are included in the National Comprehensive Cancer Network guidelines. “There are some hoops to go through, although they aren’t extraordinary,” said Alex Spira, MD, PhD, a medical oncologist with Virginia Cancer Specialists, which has offices in Fairfax and Reston. He noted that physicians should carefully justify their diagnoses. One way is by providing appropriate biomarker information, for instance. “Occasionally, you’ll get into an argument, but that’s by far the exception,” said Spira, who also holds executive committee positions at The US Oncology Network.

If an I/O therapy is intended for use in an FDA-approved indication, barriers to payment established by commercial payers can automatically dissolve, Schwartzberg said, and for a novel therapy, the wait for FDA clearance sometimes is not long, which avoids potentially protracted battles over payment. Checkpoint inhibitors are a case in point, he said. The FDA has approved 7 checkpoint inhibitors since ipilimumab (Yervoy) became the first to gain market clearance in 2011.

Getting payers to support off-label I/O treatments is much more difficult, noted Alain Algazi, MD, a medical oncologist and an associate professor of medicine with the University of California, San Francisco. “It’s pretty clear that they would prefer not to pay for expensive drugs if the drugs are not proved to help in a phase III clinical trial,” he said. One problem is that for patients with less common cancers, there may never be a phase III clinical trial. Sometimes payers approve treatment requests that are backed up with evidence from a phase IB or phase II clinical trial, but the process of gaining payer authorization remains labor intensive, Algazi said. “Have some abstracts or research papers ready if you choose to pursue off-label use of a medication.”

Figure. Tips for Gaining Payer Approvals for Immunotherapies

Familiarity With Policy is Essential

Even when a payer is willing to approve payment, more may be involved than filling out forms, Cohen noted. Oncologists may need to make phone calls for peer-to-peer review. “Most of the time, if you have a reasonable argument and you’re persistent and able to make the phone calls and get the people on the line, you’ll get to somebody at the insurance company who will listen to what you’re saying, understand it, and say, ‘That makes sense. I’ll approve it.’ Sometimes insurance companies are portrayed as the bad guy in all of this, but they do want to help patients. It’s just a matter of getting to the right person whom you can tell the story to.”

A thorough understanding of the nuances of payer clinical policies is critical, according to Sarah Hudson-DiSalle, PharmD, RPh, who serves as manager for medication assistance and reimbursement at the Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute in Columbus. Payers may require biomarker testing for some agents but not others, even when such testing is not indicated by the FDA label, she explained in a recent commentary for the Association of Community Cancer Centers.⁴ “Working within the clinical policies of third party payers is paramount to a successful foundation for payment,” she said. Payer clinical policies may include exclusion criteria, length of coverage for therapies, and past or current concurrent disease states. Although prior authorization may have been issued, practice officials need to be ready and adept at writing appeals that prove medical necessity.

Among big-ticket drugs that have seen payment approval challenges are chimeric antigen receptor (CAR) T-cell therapies, Schwartzberg said. “That’s the biggest area where we’ve seen pushback. Until recently, Medicare did not have a good payment mechanism.” The CD19-directed CAR T-cell therapy tisagenlecleucel (Kymriah) was originally approved for the treatment of relapsed/refractory pediatric and young adult patients with B-cell precursor acute lymphoblastic leukemia and has since been approved for adult patients with relapsed/refractory large B-cell lymphoma after 2 or more lines of systemic therapy. It retails for $475,000, which may not include hospitalization or follow-up care. Commercial payers have balked at paying such large price tags for therapy, Schwartzberg said. “That remains an unresolved issue.”

According to the 2018 Association of Community Cancer Centers Survey, 81% of 144 respondents said they have dedicated staff to advocate for patients on such matters as cost and insurance. Sheila Jeys, revenue cycle supervisor with Comprehensive Cancer Centers of Nevada, part of The US Oncology Network, uses a variety of strategies to fund cancer medications. In some cases, she said, “you have to get the patient involved. Sometimes payers pay more attention to them than they do to us.” She noted that in extreme cases, navigators will escalate disputes with payers by lodging complaints with the Nevada state insurance commissioner. “You just have to hold them to the fire and be stern with a lot of strong follow-up,” she added.

Smaller oncology practices may not be able to afford financial navigators, and for them, “it comes down to having the oncologist make those phone calls. Sometimes it’s hard to find the time to do that,” Cohen said. Patient assistance programs may be more fruitful. “We’ve had really good luck with them, and, hopefully, that persists, especially with the immunotherapies,” he added. However, he said, “patient income is the biggest issue that comes up with patient assistance programs. They have cutoffs. To some extent, this can be unfair. It may cost $100,000 to $150,000 a year to be treated, and that’s a lot of money even for someone who has fairly good income or a lot of assets.”

For medical oncologist Leisha A. Emens, MD, the best way to gain access to I/O drugs for women’s cancers has turned out to be through clinical trials. “That’s the ideal way,” said Emens, a Pennsylvania-based professor of medicine at the University of Pittsburgh Medical Center Hillman Cancer Center/ Magee-Womens Hospital, where she also serves as coleader of the Hillman Cancer Immunology and Immunotherapy Program and director of translational I/O with the Women’s Cancer Research Center. “It’s in a very controlled setting, and that allows us to learn the most about the agents, and ultimately, that’s how the agents will get approved.”

References

1. 2018 trending now in cancer care survey. Association of Community Cancer Centers website. accc-cancer.org/home/learn/publications/ Trends/2018-trending-now-in-cancer-care-survey. Published 2018. Accessed April 12, 2019.
2. Almutairi AR, Alkhatib NS, Oh M, et al. Economic evaluation of talimogene laherparepvec plus ipilimumab combination therapy vs ipilimumab monotherapy in patients with advanced unresectable melanoma. JAMA Dermatol. 2019;155(1):22-28. doi: 10.1001/jamadermatol.2018.3958.
3. IQVIA Institute for Human Data Science. The global use of medicine in 2019 and outlook to 2023. iqvia.com/-/media/iqvia/pdfs/institute- reports/the-global-use-of-medicine-in-2019-and-outlook-to-2023. pdf?_=1555080899579. Published January 2019. Accessed April 12, 2019.
4. Hudson-DiSalle S; Association of Community Cancer Centers Immuno-Oncology Institute. IO reimbursement: be proactive and prepared. Association of Community Cancer Centers website. accc-cancer.org/docs/immuno-oncology/io-insights/hudson-disalle- insight-2_final_no-crops.pdf?sfvrsn=3cec7cbf_2. Published November 2018. Accessed April 12, 2019.