Oral Care Evaluation to Prevent Oral Mucositis in Estrogen Receptor-Positive Metastatic Breast Cancer Patients Treated with Everolimus (Oral Care-BC): A Randomized Controlled Phase III Trial

Abstract

Background The incidence of oral mucositis (any grade) after everolimus treatment is 58% in the general population and 81% in Asian patients. This study hypothesized that professional oral care (POC) before everolimus treatment could reduce the incidence of everolimus‐induced oral mucositis. Materials and Methods This randomized, multicenter, open‐label, phase III study evaluated the efficacy of POC in preventing everolimus‐induced mucositis. Patients were randomized into POC and control groups (1:1 ratio) and received everolimus with exemestane. Patients in the POC group underwent teeth surface cleaning, scaling, and tongue cleaning before everolimus initiation and continued to receive weekly POC throughout the 8‐week treatment period. Patients in the control group brushed their own teeth and gargled with 0.9% sodium chloride solution or water. The primary endpoint was the incidence of all grades of oral mucositis. We targeted acquisition of 200 patients with a 2‐sided type I error rate of 5% and 80% power to detect 25% risk reduction. Results Between March 2015 and December 2017, we enrolled 175 women from 31 institutions, of which five did not receive the protocol treatment and were excluded. Over the 8 weeks, the incidence of grade 1 oral mucositis was significantly different between the POC group (76.5%, 62 of 82 patients) and control group (89.7%, 78 of 87 patients; p = .034). The incidence of grade 2 (severe) oral mucositis was also significantly different between the POC group (34.6%, 28 of 82 patients) and control group (54%, 47 of 87 patients; p = .015). As a result of oral mucositis, 18 (22.0%) patients in the POC group and 28 (32.2%) in the control group had to undergo everolimus dose reduction. Conclusion POC reduced the incidence and severity of oral mucositis in patients receiving everolimus and exemestane. This might be considered as a treatment option of oral care for patients undergoing this treatment. Clinical trial identification number: NCT 02069093. Implications for Practice The Oral Care‐BC trial that prophylactically used professional oral care (POC), available worldwide, did not show a greater than 25% difference in mucositis. The 12% difference in grade 1 or higher mucositis and especially the ∼20% difference in grade 2 mucositis are likely clinically meaningful to patients. POC before treatment should be considered as a treatment option of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor‐positive, HER2‐negative advanced breast cancer and metastatic breast cancer. However, POC was not adequate for prophylactic oral mucositis in these patients, and dexamethasone mouthwash prophylaxis is standard treatment before everolimus.

Oral care and oral assessment guide in breast cancer patients receiving everolimus and exemestane: Subanalysis of a randomized controlled trial (Oral Care-BC)

“…The Oral Care-BC trial showed that POC is effective in suppressing oral mucositis in breast cancer patients receiving everolims and exemestane therapy [16]. Oral care is a method that can be easily administered globally and should be considered a new standard before administering these drugs, especially in the rst 8 weeks of treatment.…”

“…A summary of the study protocol and treatment in the Oral Care-BC trial Oral Care-BC is a Japan-based, phase 3, multicenter randomized clinical trial that assessed the effectiveness of POC in preventing oral mucositis in patients treated with everolimus and exemestane for hormone receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer [8]. Patients were randomized into the POC group and the control group in a 1:1 ratio (strati ed, based on the center, use of bone-modifying agents, patient's age, and history of receiving chemotherapy within 3 months).…”

Prognostic effect of professional oral care in estrogen receptor-positive metastatic breast cancer patients treated with everolimus and exemestane enrolled in Oral Care-BC: secondary endpoint results of a randomized controlled trial

“…Patients were randomly assigned in a 1:1 ratio (strati ed according to center, use of BMA, age, and history of receiving chemotherapy within 3 months) [9]. Eligible patients were enrolled at 31 investigation sites from academic and community settings in Japan on the basis of the following key inclusion criteria: postmenopausal women having histologically or cytologically con rmed metastatic hormone-receptorpositive HER2-negative breast cancer; who were newly prescribed EVE 10 mg and EXE 25 mg; had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; and showed adequate renal function (serum creatinine level ≤1.5 × upper limit of normal).…”

“…Oral Care-BC was a phase 3 multicenter randomized clinical trial that assessed the effectiveness of professional oral care (POC) in preventing oral mucositis in patients treated with EVE and EXE for hormone-receptor-positive HER2-negative metastatic breast cancer. We previously reported that POC reduces the incidence and severity of oral mucositis in patients receiving EVE and EXE and that POC signi cantly reduces the incidence of grade 1 and 2 oral mucositis within 8 weeks [9].…”

Prognostic effect of professional oral care in estrogen receptor-positive metastatic breast cancer patients treated with everolimus and exemestane enrolled in Oral Care-BC: a randomized controlled trial

“…Oral Care-BC was a phase 3 multicenter randomized clinical trial that assessed the effectiveness of professional oral care (POC) in preventing oral mucositis in patients treated with EVE and EXE for hormone-receptor-positive HER2-negative metastatic breast cancer. We previously reported that POC reduces the incidence and severity of oral mucositis in patients receiving EVE and EXE and that POC significantly reduces the incidence of grade 1 and 2 oral mucositis within 8 weeks [9]. However, the population that has a better clinical response among patients receiving EVE and EXE was not established.…”