Design, organisation and impact of treatment optimisation studies in breast, lung and colorectal cancer: The experience of the European Organisation for Research and Treatment of Cancer

Abstract

Background: Treatment optimisation studies (TOSs) are clinical trials which aim to tackle research questions that are often left unaddressed within the current drug development paradigm due to a lack of financial and regulatory incentives to undertake them. Examples include comparative effectiveness, therapeutic sequencing and dose de-escalation studies. Trials of this nature have historically been primarily carried out by academic institutions and notfor-profit organisations such as the European Organisation for Research and Treatment of Cancer (EORTC). Objectives: Our objective was to conduct an in-depth analysis of the breast, lung and colorectal cancer TOSs that have been performed by the EORTC in the past four decades. Methods: We searched the EORTC clinical trials database for relevant studies and subsequently analysed them based on a number of predefined criteria relating to their design, organisation and scientific impact. Results: The 113 EORTC TOSs examined in this analysis were mainly standard-sized, international, multicentre phase III trials using a relatively simple, randomised, open-label design and comparing pharmacological combination regimens against standard-of-care treatments in terms of their potential to improve overall survival of patients with cancer. Although they were typically financially and/or materially supported by the industry, their legal sponsor was nearly always an independent party that did not benefit monetarily from their outcomes. If meaningful findings were obtained, their results, regardless of whether positive or negative, were published in high-impact journals, and the corresponding articles usually received a

Real-world data in oncology: a questionnaire-based analysis of the academic research landscape examining the policies and experiences of the cancer cooperative groups

“…It could also signify that the survey responders preferred to address such questions through the execution of traditional clinical trials. In any case, to definitively resolve some uncertainties, RCT-derived data are likely required, 16 , 44 , 45 , 46 which again underscores the importance of increasing the number of academia-sponsored PCTs and cmRCTs in oncology.…”

How do cancer clinicians perceive real-world data and the evidence derived therefrom? Findings from an international survey of the European Organisation for Research and Treatment of Cancer

“…For example, participants found RWD less useful for determining the optimal dose of antineoplastic drugs and for assessing their effectiveness relative to alternative interventions. It is likely that some uncertainties can only be conclusively resolved with the help of RCT-derived data (Lacombe et al, 2019a(Lacombe et al, , 2019bSaesen et al, 2020Saesen et al, , 2021, which are often difficult to generate in the post-marketing setting. The EORTC has proposed a restructuring of the current framework for developing antitumor therapies so that the evidence gaps that will be encountered by downstream decision-makers such as payers and clinicians are identified and characterized at an early stage, allowing the necessary RCTs to be initiated as soon as possible, potentially even prior to the regulatory approval (Kempf et al, 2017;Lacombe et al, 2019b;EORTC, 2020).…”

How to balance valuable innovation with affordable access to medicines in Belgium?

“…Treatment optimisation studies are clinical trials that aim to optimise the way in which therapeutic interventions are applied in real-world settings (Saesen et al, 2020). However, more structural support is needed to explore how treatment optimisation studies can be implemented into the oncology medicine development paradigm (Saesen et al, 2020;Saesen et al, 2021). The European Medicines Agency has recently established the Cancer Medicines Forum in collaboration with the European Organisation for Research and Treatment of Cancer to investigate the feasibility of this implementation (Saesen et al, 2022).…”