Pivotal trial endpoints and prices of cancer drugs in the US and Europe.

Abstract

2077 Background: A key clinical outcome for new cancer drugs is improvement in overall survival (OS), defined as time from the date of randomization to the death from any cause. However, many cancer drugs are approved by regulators based on changes to surrogate measures of OS, such as progression-free survival or overall response rate. When surrogate measures are not validated, they can provide misleading information about drug efficacy. We categorized pivotal trial endpoints for recently-approved cancer drugs in the US and Europe as showing improvements in OS vs non-OS surrogates, and evaluated the correlation with drug prices. Methods: We identified new drugs FDA-approved between 2009 and 2018 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA and Swissmedic by December 2019. Launch prices were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. Pivotal clinical trial primary endpoints were collected from the drug labeling and FDA medical reviews for the US, and the EMA public assessment reports for Europe, and categorized as OS in any trial vs. not. Pearson’s correlation tests assessed the association between launch prices and OS vs non-OS endpoints in each country. Results: 54 drugs were approved by the FDA, EMA, and Swissmedic during the study period. In the US, 30 (56%) were approved based on OS by contrast to 35 (65%) in the EMA. The number of cancer drugs approved by the FDA based on OS decreased in the past years. By contrast, the number of approved cancer drugs by the EMA based on OS were stable. There was no association for the US (p = 0.05), Germany (p = 0.13) and England (p = 0.12), while Switzerland revealed an association (p = 0.03) between OS endpoint and price. Conclusions: Reductions in use of OS endpoints as the basis for cancer drug approval in the US is concerning. Drug pricing should be better aligned with the benefit that drugs provide to patients, as measured by clinical trial outcomes such as OS.