PFS2, time from randomization to 2^nd disease progression or death, is recommended by the EMA as a surrogate for overall survival (OS), to assess effect of maintenance therapy or the impact of treatment on the efficacy of a subsequent line of therapy. The acceptance of PFS2 by reimbursement agencies is less well established.

OBJECTIVES: To evaluate the acceptance of PFS2 by national reimbursement/HTA agencies in EU5 and Canada.

METHODS: A clinicaltrials.gov database search identified cancer drug trials evaluating PFS2. The EMA SmPC for each drug was reviewed for PFS2 data. For SmPCs including PFS2 the Canadian Drug Monograph and EU5 and Canadian reimbursement agencies assessment reports were reviewed for acceptance of PFS2 data.

RESULTS: Overall, 216 trials met the search criteria, identifying 40 EMA approved drugs, 4 contained PFS2 data in the SmPC (olaparib,osimertinib,niraparib) for ovarian (OC), non-small cell lung (NSCLC, pancreatic (PC) cancer or multiple-myeloma (MM). PFS2, as a secondary-endpoint, was included in 5 NICE (OS,NSCLC) and 1 CADTH (OC) clinical assessments with mature data included in cost-effectiveness modelling and used as a surrogate for immature OS (OC). PFS2 as an exploratory-endpoint was supportive for End-of-Life status (NICE), confirmatory of the therapeutic value supporting Innovative status (AIFA) and considered patient relevant by IQWIG (NSCLC). PFS2 was not deemed to be a patient-relevant endpoint by IQWIG in any other assessment and not considered in the clinical benefit assessment by TC (MM,NSCLC,OC,PC). Data were considered immature in all AEMPS reports.

CONCLUSIONS: Although examples are limited, PFS2 as either a secondary-endpoint or an exploratory-endpoint has been accepted in reimbursement assessments. Acceptance of PFS2 data depends on data maturity, statistical-power, unmet need, relevance to clinical practice and patients. The validity of PFS2 in drug reimbursement will continue to be established with the availability of mature data and data from investigation in >200 trials.