Breakthrough Therapy Designation Criteria Identify Drugs that Improve Clinical Outcomes for Patients: A Case for More Streamlined Coverage of Promising Therapies

Grace Collins, Mark Stewart, Brittany McKelvey, Hillary Stires, Jeff Allen

Breakthrough therapy designation (BTD) is a valuable tool for expediting approval of promising therapies in oncology. Expediting drug development and review is time and resource intensive, so it is imperative to assess the performance of BTD and determine whether the criteria identify promising drugs that lead to improved outcomes for patients. This perspective provides a comparison of clinical outcomes data and National Comprehensive Cancer Network (NCCN) clinical guidelines for drugs indicated to treat non-small cell lung cancer (NSCLC) approved with BTD or without BTD between January 2013 and October 2021. Across the 31 approvals supported by data from randomized controlled trials, with the primary or co-primary endpoints of progression-free survival and/or overall survival, BTD drugs reduced the risk of death by a median of 31% and progression by a median of 48%, while drugs never receiving BTD ("Never BTD") reduced the risk of death and progression by a median of 15% and 41.9%, respectively. More BTD drugs received a NCCN recommendation in the highest category of evidence (Category 1) than Never BTD drugs, and a greater proportion of BTD drugs were considered "preferred" compared to Never BTD drugs. In the context of this improved value, we provide considerations for establishing an expedited pathway for coverage decisions on BTD drugs to support timely access for patients. These results suggest the qualifying criteria for BTD identify drugs that improve outcomes for patients with cancer, and thus, may benefit from mechanisms that expedite processes to ensure timely coverage decisions and access for patients.