The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS)

Abstract

IntroductionDuctal carcinoma in situ (DCIS) is a non-invasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials).Methods and analysisCOMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients.Ethics and disseminationThe COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for non-inferiority trials.Trial registration numberNCT02926911; Pre-results.

Association of a Diagnosis of Ductal Carcinoma In Situ With Death From Breast Cancer

“…To our knowledge, to date there is no empirical evidence that surgical treatment of DCIS reduces the subsequent mortality from breast cancer. Studies that offer a watch and wait approach, such as the Comparison of Operative versus Monitoring and Endocrine Therapy trial, 7 focus on patients with low-risk DCIS and have too few patients to evaluate mortality differences between those who undergo surgical treatment and those who do not. Given the similar SMRs for women with mastectomy and those with lumpectomy, it is possible that the mortality for women who had neither form of surgical treatment would be similar to these.…”

Association Between Time to Operation and Pathologic Stage in Ductal Carcinoma in Situ and Early-Stage Hormone Receptor-Positive Breast Cancer

“…The anxiety of nonoperative management of DCIS stems from known sampling error on core biopsy with pathologic upstaging rates ranging from 10% to 30% at the time of operation. 2,12 Although nonoperative treatment of non-high-grade DCIS is being explored in randomized clinical trials in Europe and the US (eg LORD [Low Risk DCIS], 13 LORIS [Low Risk DCIS], 14 and COMET [Comparison of Operative to Monitoring and Endocrine Therapy for Low-Risk DCIS] trials), 15 these trials are enrolling highly selected patients and have yet to report their results. In addition, retrospective data have shown that in patients meeting LORIS criteria, upstage rates at the time of operation might be 7% to 20%.…”

A medicare-based comparative mortality analysis of active surveillance in older women with DCIS

“…For example, the identification of invasion in a patient originally diagnosed with DCIS who has been undergoing AS for 2 years requires an algorithmic approach to Medicare analysis because it is not reported in SEER and cannot be directly observed in SEER-Medicare. These limitations may be addressable with data from ongoing studies aimed at determining whether some DCIS patients with fewer comorbidities may safely opt for AS 22 .…”