Value of Second-Generation TKIs Must Be Considered for CML Patients

Second-generation tyrosine kinase inhibitors (TKIs), at their current prices, are a poor treatment value as frontline treatment for patients with chronic myeloid leukemia (CML) compared with the cost and value of generic imatinib, according to the results of a modeling study.

For patients with CML, the ultimate treatment goal is to be able to discontinue TKI therapy, known as treatment-free remission. Using second-generation TKIs, such as nilotinib, dasatinib, and bosutinib, more patients with CML may be able to achieve deep molecular response more quickly. However, all of these second-generation TKIs are still on patent, with costs estimated to exceed $200,000 per year. In contrast, imatinib is available in generic formulations at a price ranging from $4,400 to $82,000 per year in the United States, with preliminary data showing safety and efficacy similar to the brand name formulation.

“The findings from our study could have a major effect on frontline therapy of chronic myeloid leukemia, on the assessment of the value of treatment-free remission, on governmental and insurance policies and coverage of different tyrosine kinase inhibitors as frontline chronic myeloid leukemia therapies, and could support lowering the cost of second-generation tyrosine kinase inhibitors,” wrote researcher Ya-Chen Tina Shih, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, in Lancet Hematology.

The researchers used a decision analytic model to look at the value of different TKI approaches from the payer perspective. In the model, about 26% of patients taking imatinib and 44% of patients taking second-generation TKIs would achieve sustained deep molecular response at 5 years. The researchers also modeled more favorable scenarios for second-generation TKIs with 66%, 88%, and 99% of patients achieving sustained deep molecular response.

For each scenario modeled, the study considered the combination of health utilities for chronic-phase CML and the annual cost of second-generation TKIs compared with generic imatinib. They considered price scenarios reflective of pricing in the United States, Europe, and developing countries. They also calculated incremental-cost effectiveness ratios (ICERs) and cost effectiveness that considered societal willingness-to-pay thresholds of $50,000 per quality-adjusted life year (QALY) for all markets and $200,000 per QALY in the United States.

In the base case scenario, which priced nilotinib at $152,814 per year, the ICER was more than $22 million. This means that it would cost society more than $22 million to achieve 1 additional QALY from replacing generic imatinib with second-generation TKIs in the frontline. According to the researchers, this meant that “second-generation TKIs as frontline therapy to achieve sustained deep molecular response was not cost-effective under either of the societal willingness-to-pay thresholds.”

Further, none of the scenarios used show a potential treatment value for second-generation TKIs at the current US pricing, or at cheaper international prices of $30,000 to $40,000 per year.

“For example, considering a scenario in the USA using second-generation TKIs vs imatinib (annual price $4,400 per year) with the potential benefit in favor of second-generation TKI (willingness to pay $200,000 per QALY, 66% of patients achieving sustained deep molecular response, and health utility of the chronic phase of 0.1), the cost of second-generation TKIs would need to be less than $25,000 per year to be a cost-effective option,” the researchers explained. “Under the same conditions in developing nations, with a price of generic imatinib of $2,100 per year and a willingness to pay of $50,000 per QALY, the annual price of second-generation TKIs should not exceed $10,000 per year of therapy.”

In an editorial that accompanied the study, Claire N. Andrews and Jeffrey Lipton, PhD, MD, of Princess Margaret Cancer Centre in Toronto, noted that until second-generation TKIs come off patent, cost-effectiveness of these drugs will continue to be an important factor when considering first-line therapy for CML.

In addition, they noted that this study did not consider costs of side-effect management, which can be greater with second-generation TKIs.

“This might mean, for example, patients developing cardiovascular conditions and going on antihypertensives and statins, which add extra costs,” they wrote.

Finally, they noted that the variation in prices of generic imatinib were “sobering.”

“As 80% of patients with chronic myeloid leukemia will never achieve a treatment-free remission, the lifetime cost of drug treatment is substantial to both the individual and society, especially in those with universal healthcare,” they wrote.