Institute for Clinical and Economic Review Report Finds Evidence Inadequate to Distinguish the Clinical Benefits of Different Antiandrogen Therapies for Men with Nonmetastatic Castration-Resistant Prostate Cancer

— Added costs of treating earlier stage disease with all therapies are aligned with their added clinical benefits for patients —

BOSTON, August 24, 2018 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of antiandrogen therapies for the treatment of nonmetastatic castration-resistant prostate cancer. The report focuses on three antiandrogen therapies: abiraterone acetate (Zytiga®; Janssen Biotech, Inc.; a separate formulation [Yonsa®; Sun Pharma] was not evaluated), enzalutamide (Xtandi®; Astellas Pharma, Inc.), and apalutamide (Erleada; Janssen Biotech, Inc.).

“While data on overall survival improvements are still immature, treating men with high-risk castration-resistant prostate cancer with antiandrogen therapies earlier, before metastatic disease is detected by conventional imaging, appears to improve outcomes,” noted David Rind, MD, MSc, ICER’s Chief Medical Officer. “Unfortunately, the lack of long-term survival data and the absence of head-to-head trials limits our ability to compare the effectiveness of enzalutamide with that of the newer drug apalutamide. For abiraterone, we have less certainty in its added benefits when used before cancer progression is detected, making it even more difficult to judge how its effectiveness matches up with the other treatment options. However, for enzalutamide and apalutamide, while there are additional costs associated with earlier treatment, those costs appear to be aligned with the clinical benefits patients receive.”

ICER did not assess the therapies’ value for treating later stage disease.

This Evidence Report will be the subject of an upcoming public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in Chicago, IL on September 13, 2018. The Midwest CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Findings 

Evidence shows a substantial net health benefit for both apalutamide and enzalutamide compared to treatment with androgen deprivation therapy (ADT) alone. However, due to a lack of direct comparisons, the evidence provides only moderate certainty that abiraterone acetate, used in combination with prednisone, achieves a small to substantial net health benefit over ADT alone.

Economic analyses assessed the long-term cost-effectiveness of apalutamide and enzalutamide, concluding that both therapies, when used to treat nonmetastatic disease, fall well within commonly accepted thresholds of $50,000-$150,000 per quality-adjusted life year compared to ADT alone.

ICER did not calculate value-based prices for these drugs, since analyses compared earlier use of the drugs to later use of the same or other drugs.

The potential budget impact for expanded use of these therapies may raise affordability concerns for health systems, depending on how broadly they are used. The FDA labeled indication is for all men with nonmetastatic castration-resistant prostate cancer, although the clinical trials looked only at a higher risk subset. Clinicians may choose to focus on treating these higher risk patients until further evidence becomes available. At current net prices, accounting for typical rebates and discounts from wholesale acquisition cost, only about 19% of eligible patients (both high and low risk) could be treated with apalutamide at its net price before spending crossed ICER’s potential budget impact threshold of $991 million per year. About 18% of patients could be treated with enzalutamide at net price before reaching the threshold.

*NOTE: This announcement was edited on 9/4/2018 to clarify Dr. Rind’s quote. The earlier version implied that ICER may have conducted a cost-effectiveness model of abiraterone; however, as shown in our Evidence Report, ICER deemed the available evidence for use of abiraterone in this population to be insufficient to make any recommendation with certainty.   

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.

Register here to attend the Midwest CEPAC meeting in person or to watch by live webcast.