Meaningful endpoints for therapies approved for hematologic malignancies

Area of Science:

• Hematology
• Oncology
• Clinical Trials
• Drug Development

Background:

• Overall survival (OS) is the standard for oncology trial efficacy but is challenging to assess in hematologic malignancies (HMs) due to long study durations and confounding subsequent therapies.
• Assessing treatment efficacy using OS is particularly difficult for novel therapies in HMs.

Purpose of the Study:

• To characterize the primary endpoints used for US Food and Drug Administration (FDA) approvals of new drugs or novel indications in HMs.
• To analyze the trends in endpoint selection for HM treatments approved between 2002 and 2015.

Main Methods:

• Retrospective analysis of FDA approvals for new drugs or novel HM indications.
• Data sourced from FDA, CenterWatch, and prescribing information.
• Reviewed 63 FDA approvals for drugs and HM indications from January 2002 to July 2015.

Main Results:

• Of 63 approvals, 71.4% used response rate (RR) and 27% used progression-free survival (PFS) or time to progression as primary endpoints.
• Only one approval included overall survival (OS).
• Median relative benefit was 71% improvement, with a median hazard ratio of 0.55 in trials with active comparators.

Conclusions:

• FDA approvals for new HM drugs often rely on endpoints like RR and PFS, not solely OS.
• Clinical benefit and treatment value assessments in HMs should incorporate RR, PFS, and other non-OS endpoints.
• This highlights the importance of diverse endpoints in evaluating novel hematologic malignancy treatments.