HOW SINGLE ARM PHASE II DATA CAN SUPPORT REIMBURSEMENT FOR ONCOLOGICS IN AUSTRALIA.

Abstract

The Food and Drug Administration (FDA) have approved 28 oncologics across 37 indications on the basis of pivotal Phase II data lacking an active comparator (Macaulay, ISPOR Toronto 2014). Approval was typically granted for indications with therapeutic alternative where a response rate ≥10% was demonstrated. This research aims to define the circumstances under which oncologics can obtain both regulatory approval and public reimbursement in Australia on this basis. Public Summary Documents (PSDs) were extracted for any oncologic indication appraised by the FDA on pivotal Phase II data and the Therapeutic Goods Administration (TGA) and Pharmaceutical Benefits Advisory Committee (PBAC) decision and key rationale were extracted. 3 oncologics across 7 oncology indications (nilotinib in chronic myelogenous leukemia, dasatinib in acute lymphoblastic leukaemia (ALL), imatinib in ALL, dermatofibrosarcoma protuberans, myelodysplastic syndrome/ myeloproliferative disease and hypereosinophilic syndrome and/or chronic eosinophilic leukemia, and aggressive mastocytosis) have been granted TGA and PBAC approval on pivotal Phase II data. 2 were TGA approved but PBAC rejected (bevacizumab and cetuximab), 3 were submitted to PBAC on Phase III data, and no PSDs were extractable for the remaining 26 indications. In 7/7 approved indications, PBAC recognized active comparator alternatives. In 4/7, the rarity of these indications was cited as a key mitigating factor. For 2/7, overall survival (OS) data was presented that indicated potentially substantial OS benefits. In 1/7, a cost-minimisation argument was accepted against a recently approved comparator. Of the PBAC-rejected drugs, cetuximab raised key concerns over a lack of OS data, while significant trial comparability issues were expressed with bevacizumab. All PBAC-approved submissions included economic modelling on a cost/benefit, not cost/QALY, approach. PBAC can recommend the reimbursement of oncologics that offer potentially substantial clinical benefits based on an indirect comparison of single arms trials with acceptable cost-effectiveness as demonstrated on a cost-benefit metric.