Abstract
Time to next treatment (TTNT) is an emerging endpoint in clinical studies of primary cutaneous T-cell lymphomas (CTCL), with utility as a surrogate marker for the “duration of clinical benefit”. TTNT provides a highly clinically meaningful endpoint that uniquely reflects not only the duration of treatment efficacy on disease and symptom control, but also incorporates the patient experience by accounting for patient compliance and tolerance to the studied therapy(s). Given the distinct challenges of pin-pointing the exact date of progression in patients with multi-compartmental CTCL, TTNT overcomes many of the shortcomings of conventional, disease-focused, clinical endpoints in primary CTCL research. Although widely accepted in clinical research for numerous other incurable malignancies, TTNT currently lacks a standardised definition. In this paper, we describe the value of TTNT as a clinical endpoint, review the applications of TTNT in primary CTCL research, and propose a standardised definition of TTNT to be applied in future clinical research of primary CTCL therapies.
Highlights
Patients with primary cutaneous T-cell lymphomas (CTCL) commonly endure high symptom burden over a lengthy clinical course, with available treatments frequently resulting in incomplete responses and risks of toxicities
We review the use of TTNT in the published CTCL literature, and propose a new standardised definition that accounts for the unique characteristics and challenges of CTCL
This definition of duration of clinical benefit (DOCB) has since proven useful in the context of subsequent prospective clinical trials [10], but is difficult to apply to retrospective studies unless the dates of initial response are rigorously defined and prospectively collected in patients’ records
Summary
Patients with primary cutaneous T-cell lymphomas (CTCL) commonly endure high symptom burden over a lengthy clinical course, with available treatments frequently resulting in incomplete responses and risks of toxicities. Defining the more subjective “duration of therapeutic benefit”, or DOCB, is challenging in CTCL This is problematic in patients with discordant treatment responses, for example, sustained resolution of pruritic stage T1/2/4 skin-disease but with development of small T3 tumour(s) would trigger a “disease progression event” despite the patient continuing to experience subjective therapeutic and symptomatic benefits. In 2015, DOCB was explored as a new endpoint in a pooled analysis of three prospective trials of low-dose TSE, using the definition of “time from initial response until the initiation of any total skin equivalent treatment (topical treatment to >50% of body surface, phototherapy, second TSE), systemic therapy, or progressive disease” [9] This definition of DOCB has since proven useful in the context of subsequent prospective clinical trials [10], but is difficult to apply to retrospective studies unless the dates of initial response are rigorously defined and prospectively collected in patients’ records. The need was recognised for a surrogate endpoint for DOCB that is and objectively measurable, with applicability to both prospective and retrospective study designs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
