Estimation of historical control rate for a single arm de-escalation study - Application to the POSITIVE trial.
Adolescent
Adult
Antineoplastic Agents, Hormonal
/ administration & dosage
Breast Neoplasms
/ drug therapy
Chemotherapy, Adjuvant
/ methods
Female
Historically Controlled Study
/ methods
Humans
Kaplan-Meier Estimate
Non-Randomized Controlled Trials as Topic
/ ethics
Pregnancy
Proportional Hazards Models
Prospective Studies
Randomized Controlled Trials as Topic
/ ethics
Receptor, ErbB-2
/ metabolism
Withholding Treatment
Young Adult
Journal
Breast (Edinburgh, Scotland)
ISSN: 1532-3080
Titre abrégé: Breast
Pays: Netherlands
ID NLM: 9213011
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
28
04
2020
revised:
28
05
2020
accepted:
29
05
2020
pubmed:
15
6
2020
medline:
30
6
2021
entrez:
15
6
2020
Statut:
ppublish
Résumé
Although randomized controlled clinical trials are optimal to evaluate the effect of an experimental therapy, single-arm trials are required whenever randomization is unethical or not feasible, such as de-escalation studies. We propose using prospectively identified historical controls to place results of single-arm, de-escalation trials into context. POSITIVE is a prospective, single-arm study in young women with hormone-receptor-positive early breast cancer to determine if temporarily interrupting adjuvant endocrine therapy in order to become pregnant increases the risk of a breast cancer event. After 272 women enrolled in POSITIVE, we identified a cohort of 1499 SOFT/TEXT patients potentially eligible to enroll in POSITIVE who did not interrupt endocrine therapy. Method I used the SOFT/TEXT cohort to calculate annualized hazard rates by a piecewise exponential model. Method II used the SOFT/TEXT cohort to group-match SOFT/TEXT patients to POSITIVE patients; sample sets of SOFT/TEXT patients were randomly drawn 5000 times to obtain sets having patient, disease, and treatment characteristics more balanced with POSITIVE participants. Compared with SOFT/TEXT, POSITIVE participants were younger, less likely to be overweight/obese, had fewer positive nodes, and fewer received aromatase inhibitor or chemotherapy. The estimated 3-year breast cancer free interval event rates were 9.5% (95% CI: 7.9%,11.1%) for Method I and 9.4% (95% CI: 7.8%,10.9%) for Method II, compared with 5.8% initially assumed when POSITIVE was designed. External control datasets should be identified before launching single-arm, de-escalation trials and methods applied during their conduct to provide context for interim monitoring and interpretation of the final analysis.
Sections du résumé
BACKGROUND
BACKGROUND
Although randomized controlled clinical trials are optimal to evaluate the effect of an experimental therapy, single-arm trials are required whenever randomization is unethical or not feasible, such as de-escalation studies. We propose using prospectively identified historical controls to place results of single-arm, de-escalation trials into context.
METHODS
METHODS
POSITIVE is a prospective, single-arm study in young women with hormone-receptor-positive early breast cancer to determine if temporarily interrupting adjuvant endocrine therapy in order to become pregnant increases the risk of a breast cancer event. After 272 women enrolled in POSITIVE, we identified a cohort of 1499 SOFT/TEXT patients potentially eligible to enroll in POSITIVE who did not interrupt endocrine therapy. Method I used the SOFT/TEXT cohort to calculate annualized hazard rates by a piecewise exponential model. Method II used the SOFT/TEXT cohort to group-match SOFT/TEXT patients to POSITIVE patients; sample sets of SOFT/TEXT patients were randomly drawn 5000 times to obtain sets having patient, disease, and treatment characteristics more balanced with POSITIVE participants.
RESULTS
RESULTS
Compared with SOFT/TEXT, POSITIVE participants were younger, less likely to be overweight/obese, had fewer positive nodes, and fewer received aromatase inhibitor or chemotherapy. The estimated 3-year breast cancer free interval event rates were 9.5% (95% CI: 7.9%,11.1%) for Method I and 9.4% (95% CI: 7.8%,10.9%) for Method II, compared with 5.8% initially assumed when POSITIVE was designed.
CONCLUSION
CONCLUSIONS
External control datasets should be identified before launching single-arm, de-escalation trials and methods applied during their conduct to provide context for interim monitoring and interpretation of the final analysis.
Identifiants
pubmed: 32535486
pii: S0960-9776(20)30119-3
doi: 10.1016/j.breast.2020.05.012
pmc: PMC7375555
pii:
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-7Subventions
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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