Comparison of operative to monitoring and endocrine therapy for low-risk DCIS (COMET study).

TPS599 Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer. However, over 97% of women are currently treated with guideline-concordant care (GCC) including surgery and/or radiation. An alternative to GCC is active surveillance (AS) which focuses on early detection of invasion rather than “treatment” of DCIS. The COMET study will compare risks and benefits of AS versus GCC in the setting of a Phase III pragmatic prospective randomized clinical trial. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI). Methods: The primary objective is to assess whether the 2-, 5-, and 7-year ipsilateral invasive breast cancer rate for AS is non-inferior to that for GCC. Secondary objectives include determining whether AS is non-inferior to GCC for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes (PROs) will enable comparison of health-related quality of life and psychosocial outcomes between GCC and AS groups at baseline, 6-months and years 1-5. Eligibility criteria include: age > 40 at diagnosis; pathologic confirmation of grade I/II DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; HER2-negative (0, 1+, or 2+ if testing performed). Following randomization to either GCC or AS, patients who decline participation will still be eligible to participate in the non-randomized cohort of the study. The planned accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites, with a projected drop-out rate of 30%, for a total of approximately 900 patients treated according to randomized arm, analyzed in an intent-to-treat analysis. Sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. The COMET trial opened in the U.S. in June 2017. To date, 50 sites have activated the trial. Comparable studies are taking place in UK (LORIS Trial) and Europe (EORTC LORD Trial); data from all three trials will be analyzed in a planned combined analysis. Clinical trial information: NCT02926911.