Meta-analysis of the efficacy of CDK4/6 inhibition in the management of metastatic HER2+/HR+ breast cancer.

e13001 Background: HER2+/HR+ breast cancer accounts for approximately 10% of all breast cancers and is often associated with CNS and visceral metastases. Resistance mechanisms involving HER2 overexpression and HR signaling limit the efficacy of targeted treatments. Novel approaches, such as CDK4/6 inhibitors, have been explored to overcome these challenges. 1 Phase III and 4 Phase II clinical trials have evaluated the efficacy of CDK4/6 inhibitors in metastatic HER2+/HR+ breast cancer. This meta-analysis synthesizes their findings to provide an efficacy assessment. Methods: A systematic literature search was conducted utilizing PubMed, Embase, and Cochrane Review to identify studies reporting CKD4/6 inhibitor use in metastatic HER2+/HR+ breast cancer. Eligible study designs included randomized clinical trials. The outcomes of interest were overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), and clinical benefit rate (CBR). A meta-analysis was performed using the R meta package. Proportions and 95% confidence intervals (CI) were calculated for each study. A random-effects model was utilized. Heterogeneity was assessed using the I 2 statistic. Results: In total, 1 Phase III and 4 Phase II RCTs were identified that had available efficacy data. Overall, 514 patients were included. The observed outcomes across the studies were as follows: ORR in 154/514 patients, CR in 5/514 patients, PR in 66/514 patients, SD in 98/514 patients, and CBR in 363/514 patients. The meta-analysis results demonstrated the following: ORR of 0.34 [0.18, 0.51] (p<0.01, I²=87.7%), CR of 0.02 [0.00, 0.12] (p<0.01, I²=79.8%), PR of 0.35 [0.17, 0.56] (p<0.01, I²=88.2%), SD of 0.40 [0.23, 0.58] (p<0.01, I²=83.2%), and CBR of 0.74 [0.53, 0.91] (p<0.01, I²=95.3%). Table 1 details the data obtained from the clinical trials. Conclusions: This meta-analysis demonstrates that CDK4/6 inhibitors are associated with promising efficacy in metastatic HER2+/HR+ breast cancer, achieving a clinical benefit rate of 74%. These findings highlight the potential role of CDK4/6 inhibition as a therapeutic strategy in this patient population. Further investigation is warranted in larger, randomized clinical trials. Efficacy outcomes reported in clinical trials evaluating CDK4/6 inhibition in metastatic HER2+/HR+ breast cancer. Study Total Treated (N) ORR (N, %) CR (N, %) PR (N, %) SD (N, %) CBR (N, %) Tolaney et al. 2020(monarcHER, Group A) 79 26 (33%) 1 (1%) 25 (32%) 36 (46%) 46 (58%) Tolaney et al. 2020(monarcHER, Group B) 79 11 (14%) 0 (0%) 11 (14%) 48 (61%) 36 (46%) Patel et al. 2023(ASPIRE) 30 22 (73%) 4 (13.3%) 18 (60%) 7 (23.3%) 29 (97%) Shagisultanova et al. 2023 27 12 (44.4%) N/A 12 (44.4%) 7 (25.9%) 19 (70.4%) Ciruelos et al. 2024 (PATRICIA, Cohort C1) 38 7 (18%) N/A N/A N/A N/A Metzger et al. 2024 (AFT-38 PATINA) 261 76 (29.2%) N/A N/A N/A 233 (89.3%)