Abstract
Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p < 0.001) and grade 3/4 AEs (OR = 1.09 vs. 2.10, p < 0.001), but no difference in risk of toxic death (OR = 1.40 vs. 1.27, p = 0.69). Differences between agents with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001). Targeted drugs with companion diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.
Highlights
The aim of personalizing cancer treatments by targeting genomic alterations in the tumor has seen rapid advances in recent years [1]
Targeted drugs with companion diagnostics are associated with improved safety, and tolerability
We identified 28 different targeted anti-cancer agents approved by the US Food and Drug Administration (FDA) for 15 different indications between January 2000 and April 2014
Summary
The aim of personalizing cancer treatments by targeting genomic alterations in the tumor has seen rapid advances in recent years [1]. Knowledge of the molecular mechanisms associated with cancer initiation and progression has recently improved with the increasing use of molecular techniques such as gene sequencing [1, 2] This knowledge has permitted the identification of alterations in cancer cells and the subsequent development of therapeutic agents targeting these alterations [3, 4]. Central to the drive for personalized medicine is the need to develop and validate specific diagnostic tests that facilitate the identification of patients that are most likely to respond to a given treatment [5] Such tests have been named companion diagnostics and are defined by the US Food and Drug Administration (FDA) as in vitro diagnostic devices that provide information that is essential for the safe and effective use of a corresponding therapeutic product [6]. Less is known about their influence on safety and tolerability of targeted anti-cancer agents
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
