FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty

J R Platt; O M Todd; P Hall; Z Craig; A Quyn; M Seymour; M Braun; J Roodhart; C Punt; N Christou; J Taieb; M Karoui; J Brown; D A Cairns; D Morton; A Gilbert; J F Seligmann

doi:10.1016/j.esmoop.2022.100642

FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty

ESMO Open. 2023 Feb;8(1):100642. doi: 10.1016/j.esmoop.2022.100642. Epub 2022 Dec 20.

Authors

J R Platt¹, O M Todd², P Hall³, Z Craig⁴, A Quyn⁵, M Seymour⁶, M Braun⁷, J Roodhart⁸, C Punt⁹, N Christou¹⁰, J Taieb¹¹, M Karoui¹², J Brown⁴, D A Cairns¹³, D Morton¹⁴, A Gilbert⁶, J F Seligmann¹⁵

Affiliations

¹ Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds. Electronic address: https://twitter.com/Jplatt_19.
² Academic Unit for Ageing and Stroke Research, University of Leeds, Leeds. Electronic address: https://twitter.com/ToddOly.
³ University of Edinburgh Cancer Research Centre, Edinburgh.
⁴ Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.
⁵ The John Goligher Colorectal Surgery Unit, St James's University Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds.
⁶ Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds.
⁷ Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester; School of Medical Sciences, University of Manchester, Manchester, UK.
⁸ Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht.
⁹ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, The Netherlands.
¹⁰ Department of Digestive Surgery, University Hospital of Limoges, Limoges. Electronic address: https://twitter.com/CNikinc.
¹¹ Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, University Paris-Cité (Paris Descartes), Paris.
¹² Department of Digestive and Oncological Surgery, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Paris Cité University, Paris, France.
¹³ Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds. Electronic address: https://twitter.com/kennycairns.
¹⁴ Institute of Cancer and Genomic Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁵ Department of Oncology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds. Electronic address: j.seligmann@leeds.ac.uk.

Abstract

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

Keywords: clinical trial; colon cancer; frailty; neoadjuvant chemotherapy; older age.

Publication types

Review

MeSH terms

Aged
Colonic Neoplasms*
Disease-Free Survival
Frailty*
Humans
Neoadjuvant Therapy / methods

Abstract

Publication types

MeSH terms

Grants and funding