OBJECTIVES: Overall survival (OS) is often considered to be the gold standard primary endpoint for demonstrating clinical efficacy in oncology trials and universally accepted by regulatory agencies. However, there are challenges to presenting mature OS data. There is growing interest in alternative endpoints like PFS2, which is also considered an accepted endpoint by many stakeholders for efficacy in clinical trials. This study assesses the relevance of PFS2 in the US healthcare system and acceptance by the FDA.

METHODS: FDA guidance for the oncology trials was reviewed to determine regulatory requirements for clinical endpoints. A US landscape assessment through secondary research was conducted to examine trends in the use of PFS2 within the US healthcare system including its application in clinical trials. The ClinicalTrials.gov database was searched to identify studies that include PFS2 within the last 5 years.

RESULTS: The latest FDA guidance outlining clinical trial endpoints for the approval of cancer drugs and biologics does not include PFS2 in its general endpoint considerations, despite published studies demonstrating a positive correlation between PFS2 and OS. Adhering to the FDA guidance, submissions for oncology drugs in the US had not previously integrated PFS2 until 2022, after which it has been leveraged as a secondary endpoint in evidence packages. ClinicalTrials.gov lists over 174 active or recruiting oncology trials, spanning January 2019 to January 2024, incorporating PFS2 as a primary or secondary endpoint.

CONCLUSIONS: Although the FDA has not formally recognized PFS2 in its guidance or historically relied on PFS2 findings for approval decisions, emerging evidence suggests its potential as a valuable secondary efficacy endpoint, leading to its increased adoption in clinical trials. While uncertainties persist, there exists a prospective opportunity to leverage PFS2 findings in future FDA submissions, pending FDA acceptance of PFS2 and the assurance of addressing potential biases and confounders adequately.