The 2016 American Society of Hematology (ASH) meeting provided insight into new treatment options and mechanism of action choices for hematologic cancers. Health plans need to continue to expand their knowledge and expertise in all cancer types to maintain the ability to manage and apply coverage criteria appropriately as FDA approvals continue to increase in oncology.
Benefit Design in Oncology
A recent movement among health plans to promote the use of medical benefit management may help assist in the adoption of new drugs, and provide a framework to support appropriate use, improved compliance, and superior outcomes for infused therapies. Data presented at the 2016 ASH meeting supports a large number of oral treatment options that will compete, replace, or augment other existing drugs, including infused and other physician-administered agents.
One of the more interesting—and perhaps disappointing—studies presented showed that an R-CHOP regimen was superior to the EPOCH-R regimen in patients with diffuse large B-cell lymphoma according to data presented by Nancy L. Bartlett, MD. Despite the hope that a newer treatment regimen could provide improvements, R-CHOP—the backbone of therapy for this patient population—was better and had a lower incidence of adverse events. The next level of studies will focus on adding biologic agents to R-CHOP in an effort to offer a superior alternative to traditional standard-of-care treatment.
Health plans should monitor the pipeline of therapies and each drug’s unique mechanism to effectively evaluate the number of newer agents on the horizon. Emerging therapies pose an interesting mix of mechanisms of action and clinical trial results to assess from an efficacy and safety perspective.
In acute myelogenous leukemia (AML), several agents with encouraging results were reported at the meeting. The investigational hedgehog signaling pathway inhibitor glasdegib demonstrated an improvement in progression-free survival when added to low-dose cytarabine in the treatment of patients with AML. Crenolanib, an oral pan-FLT-3 inhibitor, demonstrated a good overall response rate in patients with mutation-positive relapsed or refractory AML. Patients with treatment-naïve AML may benefit from the oral selective tyrosine kinase inhibitor (TKI), entospletinib, as many patients achieved a complete response to this therapy. Each of these products provides a newer mechanism of action along with comparison with current therapies with the goal to advance the science of hematologic cancer treatment.
Myelofibrosis and multiple myeloma continue to challenge investigators and health plans as new treatment options are studied with different end points to assess their clinical value. The investigational drug pacritinib showed a reduction in spleen volume as a positive clinical outcome as well as an overall improvement in symptoms for patients with myelofibrosis. This JAK1/JAK2 inhibitor will compete with ruxolitinib in the management of myelofibrosis. Although pacritinib is currently on hold by the FDA because of cardiac and hemorrhagic events, recent data may support reconsideration for this patient population. In addition, agents such as venetoclax and elotuzumab may offer improvements in relapsed or refractory or high-risk smoldering multiple myeloma.
Chimeric antigen receptor (CAR) T-cell therapy is another promising option for the treatment of aggressive lymphoma. The investigational CAR T-cell agent KTE-C19 had a 6-fold higher response in patients compared with historical controls. Sattva S. Neelapu, MD, highlighted the need for prescribers of these treatments to be educated on potential side effects related to cytokine release and neurologic events. Complete responses with KTE-C19 in the study population were durable for >1 year in 75% of the patients. Using the patient’s own T-cells and applying genetic engineering to create the therapy provides a unique patient-specific targeted approach in this difficult-to-treat population.
Health plans struggle with decisions regarding whether to halt coverage for therapies that are no longer providing clinical benefit to the patient. The study by Francois-Xavier Mahon, MD, PhD, related to dose reductions in chronic myeloid leukemia (CML) is relevant to drug benefit managers, because the opportunity to reduce TKI dose by 50% in patients who have achieved a deep molecular remission result in direct savings of 50% to the pharmacy budget for CML. A reduction in TKI dose, rather than discontinuation, is the best option, as evidenced by the EURO-SKI trial that showed 50% of patients with CML relapsed at around 15 months if treatment was stopped. Another advantage of dose reduction is a reduced rate of side effects that may require medical treatment. Although this information was not included in this trial, further studies could offer additional medical cost-savings above and beyond the drug cost-savings.
The concept of value-based care is becoming increasingly popular in discussions with at-risk providers and for health plans with financial risk for health benefits. Ohad Oren, MD, presented an intriguing approach to a new value model that includes the addition of long-term toxicity into the equation to truly assess the value of a particular oncology drug. Dr Oren suggests that long-term safety should be an important consideration in the choice of drug therapy for patients with cancer. In particular, cancers that are considered highly curable would place a patient at a greater long-term risk for drug-related toxicity because of an increased life expectancy.
Andrew Aw, MD, MEng, FRCPC, presented a cost-effectiveness study comparing conventional chemoimmunotherapy with bendamustine and rituximab that demonstrated the 2-drug combination was more cost-effective than chemoimmunotherapy. This is the type of approach that health plans will need to consider in the future in an attempt to manage and control cancer drug costs. Studies like this help to add to the body of medical literature that will support the use of appropriate utilization management in oncology.
There is also a great deal of excitement in oncology related to value frameworks, such as those created by the American Society of Clinical Oncology and the European Society for Medical Oncology, with the hope that they can help to drive care to drugs with the highest value. Matthew C. Cheung, MD, SM, FRCPC, and colleagues discovered significant variation in scoring when applying the different tools. In addition, the tools were designed for solid tumors, and extrapolation to hematologic tumors may not be effective. Health plans have a challenging task to review and evaluate the various frameworks and examine whether they can offer benefit to their oncology management programs.
Finally, the significant number of therapies in the pipeline will challenge benefit administrators and physicians to look for new ways to identify clinically efficacious, high-value, and cost-effective treatment options for patients in need of first, second, or later line therapies.
Pharmaceutical manufacturers will need to work with plan administrators to help educate them on the profiles of new agents and their appropriate placement in current guidelines or pathways. It is clear that there is tremendous opportunity with novel approaches to treatment and opportunities to assess value-based care, and, when validated, incorporate value frameworks into the field of oncology.