How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials.

Á Sanz Rubiales,M.E Sánchez-Gutiérrez,M.L Del Valle Rivero,L.A Flores Pérez

doi:10.3747/co.27.5365

Á Sanz Rubiales, M.E Sánchez-Gutiérrez + Show 2 more

Open Access

https://doi.org/10.3747/co.27.5365

Copy DOI

Journal: Current Oncology	Publication Date: May 1, 2020
Citations: 4	License type: CC BY 4.0

Abstract

In 2012, 11 standards describing best supportive care (bsc) in clinical trials in advanced cancer were defined through consensus statements. The consensus included 15 key components. Our objective was to analyze whether clinical trials that involved patients with advanced cancer and that included bsc in at least 1 arm met the standards and contained the key components. We reviewed clinical trials registered in ClinicalTrials.gov, the isrctn (International Standard Randomised Controlled Trial Number) registry, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform for 2012-2018. We selected only phase iii studies in patients with advanced cancer that included bsc in at least 1 arm. We describe the characteristics of the trials, together with the definition and components of bsc. We analyzed how the trials met the standards and adopted the key components of bsc. Of 193 trials retrieved, only 64 met the inclusion criteria; 36 of those trials (56%) had no definition of bsc. Less than 7% of the trials included even 3 of the 8 bsc standards that were defined to be included in the design of trials. Furthermore, trials mentioned only 5 of the 15 key components that the consensus defined to be fundamental, with symptom management appearing in 22% of trials and the other 4 components appearing in less than 8%. Most clinical trials registered during 2012-2018 that involved patients with cancer and an arm with bsc did not define the bsc concept. Hence, the design of those trials does not meet the consensus recommendations.

Highlights

There are three neurotrophic tyrosine receptor kinase (NTRK) genes, NTRK1, NTRK2, and NTRK3, which encode the tyrosine receptor kinase (TRK) receptors, TRKA, TRKB, and TRKC, respectively [1,2,3]
Differentiated thyroid carcinoma and MTC are somewhat unique from the other tumour types discussed, in that, for cases not cured by surgery +/− radioactive iodine (RAI), the typical disease course progresses slowly [36]
We suggest testing all patients with next generation sequencing (NGS) without a pan-TRK IHC screen, because pan-TRK IHC screening is associated with faint staining in gastrointestinal stromal tumours (GISTs) and can be challenging to interpret, and the volume of patients in this category would be low [111]

Summary

Introduction

There are three neurotrophic tyrosine receptor kinase (NTRK) genes, NTRK1, NTRK2, and NTRK3, which encode the tyrosine receptor kinase (TRK) receptors, TRKA, TRKB, and TRKC, respectively [1,2,3]. For patients with metastatic CRC who are eligible for first-line therapy (estimated 75% of patients diagnosed each year), tumour IHC testing for mismatch repair deficiency (dMMR) and NGS testing for extended RAS and BRAF mutations is the standard clinical practice. While it would be ideal for NTRK1-3 gene fusions testing to be incorporated into this routine panel, this is currently not cost-effective or feasible at many centres. Some cases of KIT/PDGFRA wildtype tumours have been shown to harbour an NTRK gene fusion [100] Whether these are true GISTs or rather a completely distinct group of gastrointestinal mesenchymal tumours will need to be studied further [100]. There is considerable variability in treatment response to current standards of care across histologies

Objectives

Methods

Findings

Conclusion