Estimated Medicare Spending on Cancer Drug Indications With a Confirmed Lack of Clinical Benefit After US Food and Drug Administration Accelerated
- Medicare Parts B and D spent at least $569 million between 2017 and 2019 on 10 cancer drug indications without confirmed overall survival (OS) benefit after accelerated approval (AA).
- Approximately $224 million was spent on drug indications that were either voluntarily withdrawn or recommended for withdrawal by the ODAC.
- Spending on remaining AA indications may increase unless the FDA revokes these indications.
- The FDA should balance early access to potentially effective drugs with associated risks and enforce timely completion of confirmatory trials.
- The FDA should consider withdrawing AA drugs lacking OS benefit or high-quality evidence, and revisit the approval status of AA drugs with surrogate endpoint-based trials.
- Study limitations include reliance on ICD-10 codes and a cohort of Medicare Advantage enrollees to estimate spending, which may not reflect all public or commercial insurance populations.
- The study underscores the need for timely FDA action to withdraw drug indications with confirmed lack of clinical benefit.
The accelerated approval (AA) pathway expedites the market entry of new drugs by allowing the US Food and Drug Administration (FDA) to grant approval using surrogate end points (eg, progression-free survival) that are “reasonably likely” to predict clinical benefit (eg, overall survival [OS]). Drug manufacturers are required to confirm clinical benefit after approval.
Since December 2020, the FDA has reevaluated 10 AA indications with a confirmed lack of OS benefit of 4 drugs used to treat cancer: atezolizumab (breast and urothelial [cisplatin-ineligible and cisplatin-eligible] cancer), durvalumab (urothelial cancer), nivolumab (hepatocellular and lung cancer), and pembrolizumab (gastric, hepatocellular, lung, and urothelial cancer). This reevaluation resulted in voluntary manufacturer withdrawals of atezolizumab for urothelial cancer, durvalumab for urothelial cancer, and nivolumab and pembrolizumab for lung cancer. In April 2021, the FDA Oncologic Drugs Advisory Committee (ODAC) considered the approval status of the 6 remaining AA indications. The ODAC members voted to withdraw 2 indications (pembrolizumab for gastric cancer and nivolumab for hepatocellular cancer), and they cited poor trial designs and the lack of other treatment options as reasons for retaining the remaining 4 indications (atezolizumab for breast and urothelial [cisplatin-ineligible] cancer and pembrolizumab for hepatocellular and urothelial cancer). Although the FDA is not obliged to follow ODAC recommendations, it typically does so.
