Abstract PO3-04-03: Drug Holidays in Patients with HER-2 Positive Metastatic Breast Cancer

Abstract Background Treatment of HER-2 positive metastatic breast cancer (MBC) involves the use of HER-2-targeted therapy in combination with cytotoxic chemotherapy and/or hormone therapy. Treatment duration for HER2-targeted agents is not standardized, and patients are often kept on these drugs indefinitely. Drug holidays can be initiated due to poor tolerance of drug or can be considered when trying to limit drug toxicity. Our study aims to determine the safety of utilizing drug holidays for patients receiving HER2-targeted therapies and the effect on overall survival and disease progression. Methods Study Design This retrospective study included patients who were diagnosed with metastatic HER2 positive breast cancer and had complete clinical and survival data available within UPMC Magee Women’s Hospital. The patients were divided into two groups based on whether they had a drug holiday or not. A drug holiday was defined as the temporary cessation of antiHER2 therapy for a minimum of three months in patients receiving HER2-targeted treatments. This involved the discontinuation of earlier- and later-line medications without considering the cessation of hormone therapy. Statistical Analysis 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. The results were reported as proportions for categorical variables and as medians with 25th-75th percentiles for continuous variables. Survival rates and Hazard ratios were estimated using Kaplan-Meier log-rank tests and Cox models, respectively. The significance level was set at p < 0.05 for all analyses. Results 83 patients with HER2+ MBC treated with HER2-targeted therapy were identified, of which 54 patients were in the drug holiday group. Of noted patient variables, there was no significant difference in the tumor histology, distribution of estrogen receptor (ER) status (p= 0.38) and progesterone receptor (PR) status (p = 0.64). The use of hormonotherapy, immunotherapy, radiotherapy to the primary tumor, and radiotherapy to metastasis did not significantly differ between the two groups (p > 0.05 for all comparisons). Subgroup analysis was conducted within the hormonotherapy subgroup to assess the survival difference in the no drug holiday group and to evaluate the impact of drug holiday on antiHER2 therapy cessation while continuing hormonotherapy. There was a trend towards a higher proportion of patients who were deceased in the no drug holiday group (62%) compared to the drug holiday group (42%), although this difference did not reach statistical significance (p = 0.16). The disease status differed significantly between the two groups (p < 0.0001). In the no-drug holiday group, 72% of patients had progressive disease, while 20% had stable disease with the anti-HER2 therapy and 7% had no-evidence of disease. In contrast, the drug holiday group had a higher proportion of patients with no-evidence of disease (48%) compared to progressive disease (38%) and stable disease (14%). The drug holiday group demonstrated higher overall survival (61% with median follow-up 1719 days 25th-75th percentile: 963-2222) compared to the no drug holiday group (39% with median follow-up time of 803 days 25th-75th percentile: 216-1510) (p= 0.04). Conclusion Overall, our findings suggest that utilization of a drug holiday in stable and NED HER2+ MBC is not associated with decreased survival. Analysis within the hormonotherapy subgroup indicated no survival difference in the drug holiday group, highlighting the potential for cessation of antiHER2 therapy while continuing hormonotherapy in this specific subgroup. However further prospective studies with long drug holiday intervals, larger sample size, and control of other potential confounding factors are needed to validate these results. Citation Format: Saba Kurtom, Kazim Senol, Qurat Ul Ain Sabih, Efe Sezgin, Adam Brufsky, Vikram Gorantla, Shannon Puhalla, Atilla Soran. Drug Holidays in Patients with HER-2 Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-03.