Keywords: maintenance, confounding, design, feasibility, regulatory
It is well-known that many cancers will invariably progress following initial response to treatment. Since newer targeted cancer drugs often have fewer side effects than standard chemotherapy, use of maintenance therapy to prevent or delay cancer progression or slow cancer growth is increasingly being considered as an option in cancer care. Maintenance trials are currently being conducted despite a lack of consensus on appropriate design. It is often hard to interpret the results of these trials due to confounding effects such as patient drop out, pre-treatment, and crossover to alternative treatments. The need to correctly frame the clinical question of interest, and then answer it with a design that appropriately balances statistical rigor with logistical feasibility, is paramount. This roundtable will discuss the challenges associated with the design and conduct of maintenance studies. The goal would be for pharma statisticians to compare notes and share their experiences with maintenance studies, as well as, get the regulatory perspective on such studies from participating FDA statisticians.
Some key questions/talking points for discussion:
1. How do we strike a balance between ‘ideal’ designs and ‘feasible’ designs when trying to answer a maintenance question?
2. Are only gold standard endpoints like overall survival (OS) and progression-free-survival (PFS) relevant for maintenance, or, can alternative endpoints such as minimum residual disease (MRD) be considered?
3. How (if at all) should designs differ based on length of treatment in maintenance (e.g. continuous treatment until progression versus treatment for a pre-determined fixed period of time)?