Arif Manji1, Irene Brana, Eitan Amir, George Tomlinson, Ian F Tannock, Philippe L Bedard, Amit Oza, Lillian L Siu, Albiruni R Abdul Razak. 1. Arif Manji, Irene Brana, Eitan Amir, Ian F. Tannock, Philippe L. Bedard, Amit Oza, Lillian L. Siu, and Albiruni R. Abdul Razak, Princess Margaret Cancer Centre, University Health Network; George Tomlinson, University of Toronto; and Arif Manji, Hospital for Sick Children, Toronto, and Southlake Regional Health Centre, Newmarket, Ontario, Canada.
Abstract
PURPOSE: To evaluate the use and objectives of expansion cohorts in phase I cancer trials and to explore trial characteristics associated with their use. METHODS: We performed a systematic review of MEDLINE and EMBASE, limiting studies to single-agent phase I trials recruiting adults and published after 2006. Eligibility assessment and data extraction were performed by two reviewers. Data were assessed descriptively, and associations were tested by univariable and multivariable logistic regression. RESULTS: We identified 611 unique phase I cancer trials, of which 149 (24%) included an expansion cohort. The trials were significantly more likely to use an expansion cohort if they were published more recently, were multicenter, or evaluated a noncytotoxic agent. Objectives of the expansion cohort were reported in 74% of trials. In these trials, safety (80%), efficacy (45%), pharmacokinetics (28%), pharmacodynamics (23%), and patient enrichment (14%) were cited as objectives. Among expansion cohorts with safety objectives, the recommended phase II dose was modified in 13% and new toxicities were described in 54% of trials. Among trials aimed at assessing efficacy, only 11% demonstrated antitumor activity assessed by response criteria that was not previously observed during dose escalation. CONCLUSION: The utilization of expansion cohorts has increased with time. Safety and efficacy are common objectives, but 26% fail to report explicit aims. Expansion cohorts may provide useful supplementary data for phase I trials, particularly with regard to toxicity and definition of recommended dose for phase II studies.
PURPOSE: To evaluate the use and objectives of expansion cohorts in phase I cancer trials and to explore trial characteristics associated with their use. METHODS: We performed a systematic review of MEDLINE and EMBASE, limiting studies to single-agent phase I trials recruiting adults and published after 2006. Eligibility assessment and data extraction were performed by two reviewers. Data were assessed descriptively, and associations were tested by univariable and multivariable logistic regression. RESULTS: We identified 611 unique phase I cancer trials, of which 149 (24%) included an expansion cohort. The trials were significantly more likely to use an expansion cohort if they were published more recently, were multicenter, or evaluated a noncytotoxic agent. Objectives of the expansion cohort were reported in 74% of trials. In these trials, safety (80%), efficacy (45%), pharmacokinetics (28%), pharmacodynamics (23%), and patient enrichment (14%) were cited as objectives. Among expansion cohorts with safety objectives, the recommended phase II dose was modified in 13% and new toxicities were described in 54% of trials. Among trials aimed at assessing efficacy, only 11% demonstrated antitumor activity assessed by response criteria that was not previously observed during dose escalation. CONCLUSION: The utilization of expansion cohorts has increased with time. Safety and efficacy are common objectives, but 26% fail to report explicit aims. Expansion cohorts may provide useful supplementary data for phase I trials, particularly with regard to toxicity and definition of recommended dose for phase II studies.
Authors: Lucas Moreno; Andrew D J Pearson; Xavier Paoletti; Irene Jimenez; Birgit Geoerger; Pamela R Kearns; C Michel Zwaan; Francois Doz; Andre Baruchel; Josef Vormoor; Michela Casanova; Stefan M Pfister; Bruce Morland; Gilles Vassal Journal: Nat Rev Clin Oncol Date: 2017-05-16 Impact factor: 66.675
Authors: Daniel Morgensztern; Meghan J Campo; Suzanne E Dahlberg; Robert C Doebele; Edward Garon; David E Gerber; Sarah B Goldberg; Peter S Hammerman; Rebecca S Heist; Thomas Hensing; Leora Horn; Suresh S Ramalingam; Charles M Rudin; Ravi Salgia; Lecia V Sequist; Alice T Shaw; George R Simon; Neeta Somaiah; David R Spigel; John Wrangle; David Johnson; Roy S Herbst; Paul Bunn; Ramaswamy Govindan Journal: J Thorac Oncol Date: 2015-01 Impact factor: 15.609