546P Innovative medicine in rare cancer: Perceived value of adaptive trials and surrogate endpoints for clinical decisions


      Rare cancers (RC) account for up to 20% of new cancer cases and Innovative Medicinal Products (InMP) are required to address this high unmet medical need. Adaptive trials may be an alternative to large randomized controlled trials (RCT) for InMP development to target RC patients. Despite recommendation and endorsement by competent authorities and medical societies, the number of adaptive phase II/III trials in RC needs to be improved, with better understanding of their value for clinical decisions in daily practice.


      A literature search and on-line survey of RC oncologists was initiated in March 2020. Participants were questioned on the importance of different evidence levels, types of adaptive trial design, and categories of surrogate endpoints for clinical decisions in RC. Attributes were rated on a 5-point scale from 1 not important/strongly disagree to 5 very important/strongly agree.


      Analysis of first responders showed that evidence from phase II/III clinical trials and comprehensive knowledge of InMP characteristics was considered of high value (rated as important, fairly important and very important) by 95% and 98% of responders respectively, followed by patient reported outcomes (86%). For clinical decisions in RC, evidence from phase II/III trials with an adaptive design and relatively small sample size was considered high value by 97% of responders, followed by conventional RCT (82%). Surrogate endpoints, such as time-to-first-subsequent treatment (TFST), time-to-second progression (PFS2), or time-to-second-subsequent treatment (TSST) were considered valuable alternatives to overall survival (OS) by 80% of oncologists, along with progression-free-survival (PFS). Futility analysis and/or interim analysis, adaptive sample size and adaptive randomization were perceived as more important than seamless design or adaptive patient population.


      Practicing RC oncologists rate evidence from adaptive clinical trials with as high value and importance for clinical decision processes as RCT. Pharmaceutical companies developing InMP for RC patients should consider surrogate endpoints (TFST, PFS2 and TSST) in adaptive phase II/III trials as appropriate alternatives to OS.

      Legal entity responsible for the study

      The authors.


      Has not received any funding.


      A. Krendyukov: Leadership role, Full/Part-time employment: Apogenix AG. M. Zabransky: Full/Part-time employment: Hexal AG. S. Singhvi: Leadership role, Full/Part-time employment: System Analytic Limited.