Oncologic Drugs Approval in Europe for Solid Tumors: Overview of the Last 6 Years.

Abstract

Simple SummaryWe present a systematic overview of EMA-approved oncologic drugs, both as new or extensions of indications, over 6 years, from 2015 to 2020. Our analysis confirms a long-standing trend in drug development for which most of the efforts led to broadening indications of pre-existing molecules, with immunotherapy and signal transduction inhibitors contending the leadership. Many drugs with the same or a very similar mechanism of action are approved for the same indication without a direct head-to-head comparison. Moreover, we show that the majority of drugs entered the market without evidence of overall survival or quality of life benefit but based on surrogate outcomes. Our data support some considerations about the modern drug development in oncology, where the goal is to provide the patients with the fastest possible access to new drugs. The debate on the optimal methodology to develop new drugs remains an unmet need.(1) Background: Drug development in oncology is changing rapidly. The aim of the present study was to provide an insight into the features of anti-tumor drugs approved in Europe; (2) Methods: We included all the indications for solid tumors issued by the European Medicines Agency (EMA) between 2015 and 2020. We extracted data from European Public Assessments Reports (EPAR), including drug name, mechanism of action, setting, features of pivotal clinical trials, primary end-points, quality of life (QoL); (3) Results: In the explored period, EMA issued 132 new indications (81 indications’ extensions) for 62 oncology drugs. In about half of indications (47%), the approval was biomarker-based. Immune check point inhibitors (ICIs) and signal transduction inhibitors were the two most representative drug categories (62%). Most of the indications were for the advanced setting (91%) and front-line therapy (66%). The most common tumor types were non-small cell lung cancer (24%), breast (16%), and melanoma (10%). Two thirds of the indications (73%) were approved based on phase III trials. Overall survival (OS) represented the primary end-point only in 39% of indications, mainly limited to advanced setting (98%) and ICI trials (80%). Almost all (94%) cell cycle and DNA repair mechanism inhibitors were approved based on progression free survival (PFS) data. In pivotal trials with signal transduction inhibitors, objective response rate (ORR) was the prevalent (45%) primary end-point. QoL was never considered as primary end-point; (4) Conclusions: In this analysis, we intended to offer an updated picture of the recent drug development in oncology. Most of the efforts led to broadening indications of pre-existing molecules, with signal transduction inhibitor and ICIs contending the leadership. Twenty-seven percent of the indication were approved without a phase III trial. The majority of drugs entered the market without evidence of OS or QoL benefit but based on surrogate outcomes.