84 Exceptional Responders in De Novo Metastatic Breast Cancer (dnMBC) Drug Cessation in Patients With HER2-Positive Metastatic Breast Cancer; Multicenter Retrospective Study

Background

Treatment duration for HER2-targeted agents is not standardized, and patients are often kept on these drugs indefinitely in stage IV HER2-positive (HER2+) breast cancer. Our group previously presented that utilization of a drug holiday in stable and no evidence of disease (NED) HER2+ de novo metastatic breast cancer is not associated with decreased survival compared with patients who do not take a drug holiday. In this retrospective study, we hypothesize that exceptional responders (ExR) may be able to take an extended drug cessation.

Methods

This multicenter, retrospective study included patients who were diagnosed with de novo HER2+ metastatic breast cancer and had complete clinical and survival data available. All patients had a drug cessation, which was defined as ceasing anti-HER2 therapy for at least 3 months in patients receiving HER2-targeted therapies. Treatment response was evaluated as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1. Patients with CR and PR were categorized as ExR. The chi-square test or Fisher's exact test was used to compare categorical variables, and the Mann-Whitney U test was used to compare continuous variables. Survival rates were estimated using Kaplan Meier log-rank tests and Cox models. The significance level was P < .05 for all analyses.

Results

There were 35 patients with HER2+ metastatic breast cancer treated with HER2-targeted therapies who had drug cessation included. Mean age was 57.7 ± 12.4, median follow up was 79 months (range, 13-194) and median drug cessation time was 14 months (range, 3-121). Drug cessation reasons were toxicity in 15 (43%) patients, patient preference in 14 (40%) patients, and physician decision in 6 (17%) patients. Ten (29%) patients were premenopausal, tumors were invasive ductal cancer in 32 (91%) patients, 20 (57%) patients had estrogen receptor–positive tumors, 10 (29%) patients had bone-only metastases, 13 (37%) patients received radiation therapy to metastasis sites, and breast surgery was done in 14 (40%) patients. CR was seen in 18 (51%) patients and PR in 3 (9%) patients. Nine (26%) patients died: 2 (10%) among ExR patients and 7 (50%) among non-ExR patients (P = .001). Mean survival was 171 months (95% CI, 144.35-199.11) in the ExR group compared to 84.6 months (95% CI, 62.41-106.79) in the non-ExR group (P = .001) (Figure). Twelve (86%) patients (12/14) in the surgery group and 14 (67%) patients (14/21) in the non-surgery group are still alive.

Conclusion

While we await the results of the STOP-HER2 phase 2 clinical trial, the NCI exceptional responders' initiative, and the CHLOE trials, our analysis suggests that extended drug cessation is feasible in patients with HER2+ de novo metastatic breast cancer who are ExR.