OBJECTIVES: Access to approved cancer treatments based on progression-free survival (PFS) may face reimbursement challenges when cancers have prolonged post-progression survival and overall survival (OS) outcomes are immature. Post-progression endpoints (PPEs) may offer clinically meaningful and patient-relevant data for regulatory and reimbursement decision-making. We analyzed clinical trials with PPEs from 01/2008 to 04/2019, and evaluated their influence on regulatory and health technology assessment (HTA) reviews.

METHODS: Clinical trials with PPEs such as PFS2, time to first subsequent therapy (TFST), and time to second subsequent therapy (TSST) were reviewed from clinicaltrials.gov, EU Clinical Trials Register, and TrialTrove. Analyses were limited to studies in cancer identified by ‘Trial status’ (planned, open, closed, completed), ‘Trial phase’ (phase 2, 2/3, and 3), ‘Sponsor type’ (industry only), and for patient with metastatic or early stage solid tumors or hematologic malignancies.

RESULTS: Of more than 8,300 studies, 235 were identified with PPEs as either primary (7%), secondary (70%), exploratory (2%), or other endpoints (21%). PPEs were most frequently identified in ovarian (17%), multiple myeloma (15%), NSCLC (13%), colorectal (10%), prostate (10%) and breast (8.5%) cancer studies. PFS2, TSFT, and TSST were reported as endpoints in 80%, 27%, and 18% of studies, respectively. 14 studies served as the basis for marketing authorization reviews by the FDA or EMA and 9 studies were reviewed by EU HTA/reimbursement agencies. The utility of PPEs in regulatory and reimbursement reviews were supplemental to traditional endpoints in these assessments.

CONCLUSIONS: Use of PPEs in clinical trials in cancer is increasing and is supplementing traditional efficacy endpoints. Their utility in regulatory and reimbursement decision-making are still in an emergent stage, but may provide additional value of oncology product efficacy and cost-effectiveness.