Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2024-12
• Main Authors: Hwang, E. Shelley, Hyslop, Terry, Lynch, Thomas, Ryser, Marc D, Weiss, Anna, Wolf, Anna, Norris, Kelsey, Witten, Meredith, Grimm, Lars, Schnitt, Stuart, Badve, Sunil, Factor, Rachel, Frank, Elizabeth, Collyar, Deborah, Basila, Desiree, Pinto, Donna, Watson, Mark A, West, Robert, Davies, Louise, Donovan, Jenny L, Shimada, Ayako, Li, Yutong, Li, Yan, Bennett, Antonia V, Rosenberg, Shoshana, Marks, Jeffrey, Winer, Eric, Boisvert, Marc, Giuliano, Armando, Larson, Kelsey E, Yost, Kathleen, McAuliffe, Priscilla F, Krie, Amy, Tamirisa, Nina, Carey, Lisa A, Thompson, Alastair M, Partridge, Ann H
• Format: Article
• Language: English
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2024.26698

IMPORTANCE: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown. OBJECTIVE: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care. DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor–positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023. INTERVENTIONS: Participants were randomized to receive active monitoring (follow-up every 6 months with breast imaging and physical examination; n = 484) or guideline-concordant care (surgery with or without radiation therapy; n = 473). MAIN OUTCOMES AND MEASURES: The primary outcome was 2-year cumulative risk of ipsilateral invasive cancer diagnosis, according to planned intention-to-treat and per-protocol analyses, with a noninferiority bound of 0.05%. RESULTS: The median age of the 957 participants analyzed was 63.6 (95% CI, 55.5-70.5) years in the guideline-concordant care group and 63.7 (95% CI, 60.0-71.6) years in the active monitoring group. Overall, 15.7% of participants were Black and 75.0% were White. In this prespecified primary analysis, median follow-up was 36.9 months; 346 patients had surgery for DCIS, 264 in the guideline-concordant care group and 82 in the active monitoring group. Forty-six women were diagnosed with invasive cancer, 19 in the active monitoring group and 27 in the guideline-concordant care group. The 2-year Kaplan-Meier cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group vs 5.9% in the guideline-concordant care group, a difference of −1.7% (upper limit of the 95% CI, 0.95%), indicating that active monitoring is not inferior to guideline-concordant care. Invasive tumor characteristics did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Women with low-risk DCIS randomized to active monitoring did not have a higher rate of invasive cancer in the same breast at 2 years compared with those randomized to guideline-concordant care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02926911