Early Endpoints in Oncology: Increasingly Common in Clinical Trials Yet Frequently Challenged in Health Technology Appraisals (HTAs)

ISSUE: In recent years, more and more regulatory approvals in oncology are based on improvements in early endpoints (e.g. progression free survival, response rate) with the goal of bringing new innovative treatments faster to cancer patients. However, early endpoints are frequently challenged in HTAs with continued preferences for final endpoints (overall survival) or certainty of benefit on final endpoints either through long-term follow up or validation of the early endpoints as a surrogate for overall survival. This often leads to delays in access and reimbursement of new oncology drugs. Meanwhile, the evidence required for surrogate endpoints validation varies across HTA bodies and the success in surrogate endpoint validation in oncology is rare.

OVERVIEW: Dr. Sasane will introduce the issue and panelists (5 min). Ms Zheng will represent the drug developer’s perspective on the rationale of using early endpoints as primary efficacy endpoints in oncology trials, including changing treatment landscape, feasibility challenges of using overall survival as the sole primary endpoint, value of early access to innovative therapy, the patient-relevance of early endpoints and the practical challenges of surrogate endpoint validation (13 min). Dr. Latimer will share the HTA perspective on key concerns of making HTA recommendations based on early endpoints with immature OS data and where surrogate endpoint validation may be insufficient to address reimbursement questions (13 min). Ms. Cope will provide her research perspective and propose a stepwise framework to assess the feasibility of surrogacy meta-analysis to ensure underlying assumptions are explored systematically in anticipation of HTA requirements (14 min). There will be 15 mins to address audience questions and debates. The panel hopes to benefit the three types of stakeholders represented by the panelists to facilitate future policy and research initiatives to improve the understanding and robustness of early endpoints in reimbursement decision-making.