Comparing an operation tomonitoring, with or without endocrine therapy (COMET): Aprospective randomized trial for low-risk DCIS (AFT-25)
Cancer Research
; 81(4 SUPPL), 2021.
Article
in English
| EMBASE | ID: covidwho-1186385
ABSTRACT
Background:
Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS)annually. Without treatment, it is estimated that 20-30% of DCIS will lead to invasive breast cancer. Currently, morethan 97% of women undergo surgery, with many also undergoing radiation. An alternative to surgery for low-riskDCIS is active monitoring (AM), an approach in which regularly scheduled mammography and physical exams areused to monitor breast changes and determine if, or when, surgery is needed. Trialdesign:
COMET, a multicenterphase III prospective randomized trial, opened in the U.S. in June 2017 (clinicaltrials.gov reference NCT02926911).The hypothesis is that management of low-risk DCIS using an AM approach does not yield inferior invasive breastcancer and/or quality of life outcomes compared to surgery. Eligibility criteria Patients with a new diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS, or atypia verging on DCIS are eligible. Patients mustbe ≥40 years of age, have no contraindication for surgery, and pathologic confirmation of grade I/II DCIS. DCIS mustbe ER and/or PR≥ 10% and HER2-negative without invasion, diagnosed within 120 days of registration. Breasttissue, blood and imaging are collected at trial entry and if invasive cancer subsequently occurs, and are stored incentral repositories. Specificaims:
The primary aim is to assess whether the 2-yr ipsilateral invasive breast cancerrate for AM is non-inferior to surgery. Secondary aims include comparison of 2-, 5-, and 10-yr mastectomy rate, contralateral invasive breast cancer rate, overall survival and invasive breast cancer-specific survival, as well as 5-and 10-yr ipsilateral invasive breast cancer rate between groups. Patient reported outcomes (PRO) using validatedtools are critical secondary endpoints, and will enable comparison of health-related quality of life and psychosocialoutcomes between surgery and AM groups at prespecified time points over a period of 5 years. Statisticalmethods:
An accrual goal of 1200 was estimated using a 2-group test of noninferiority of proportions, with the 2-yrinvasive breast cancer rate in the surgery group assumed to be 0.10, including accounting for upstaging. Theprojected drop-out rate is 25%, for a total of 900 patients treated per allocation arm. The non-inferiority boundarywas set at 0.05. Based on a 1-sided un-pooled z-test, with alpha=0.05, a sample size of n=446 per group will have80% power to detect the specified noninferiority margin. Intention-to-treat analysis of the 2-yr invasive breast cancerrate will be conducted using all patients as randomized, and will be completed using Kaplan-Meier estimates,stratified by group, combined with Greenwood's confidence interval. Several sensitivity analyses (per protocol, as-treated, and instrumental variable) are also planned to account for loss of follow-up, rejection of randomizationallocation and withdrawals. Present and target accrual Trial accrual as of 7/1/20 is 540 randomized patients from84 activated Alliance for Clinical Trials in Oncology sites. Despite logistical challenges posed by the COVID-19crisis, patients continue to be recruited to the COMET trial. Over 80% of patients have sample sets/images stored inthe tissue and image repositories. This trial will provide definitive clinical, quality of life and biomarker evidenceregarding the trade-offs of surgery vs AM in patients with low-risk DCIS.
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Cancer Research
Year:
2021
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS