Antibody-drug conjugate monotherapy refines the oncological efficacy as compared to therapy of physicians' choices in advanced breast cancers: a systematic review and meta-analysis

Background: Antibody-drug conjugate (ADC) is an emerging therapy that bestows advanced breast tumors with encouraging clinical activity and manageable toxicity; however, the outcomes of phase 2/3 randomized controlled trials (RCTs) are heterogeneous. Our study aims to assess the clinical utilities [i.e., objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS)], and treatment-related adverse events (AEs) of ADC monotherapy (defined as the study cohort) versus the therapy of physician's choice (TPC) (defined as the control cohort) in participants with advanced breast tumors. Methods: We conducted a computerized retrieval to identify RCTs from MEDLINE, Web of Science, Cochrane Library, Embase databases, and ClinicalTrials.gov until April 4(th), 2023. Screening, data extraction, and quality assessment were performed in duplicate. Results: A total of 10 RCTs were involved, with 5,089 unique patients. A binary random-effect model Mantel- Haenszel method was employed to pool data due to the considerable heterogeneity. The primary outcome measure was odds ratio (OR) with the corresponding 95% confidential interval (CI) of ORR and CBR. The secondary outcome measure represented hazard ratio (HR) of PFS and OS and OR of the frequency of any grade/grade >= 3 AEs. The pooled results showed an insignificant difference of ORR (OR =1.64; 95% CI: 0.86-3.13; P=0.136) and CBR (OR =1.43; 95% CI: 0.89-2.31; P=0.142) in the study cohort than the control cohort. The pooled effect on PFS (HR =0.62; 95% CI: 0.50-0.74; P<0.001) and on OS (HR =0.70; 95% CI: 0.57-0.83; P<0.001) both indicated a significant superiority of the study cohort. The frequency of any grade AEs (OR =1.03; 95% CI: 0.75-1.41; P=0.849) and that of grade >= 3 AEs (OR =0.83; 95% CI: 0.57-1.21; P=0.342) were both observed a nonsignificant difference between the cohorts. These domains, i.e., allocation concealment, blinding of participants and personnel, and blinding of outcome assessment, had the high risk of bias over 50%. Conclusions: Compared to physician's choice, ADC monotherapy overall confirms a considerable refinement in survival benefits plus a similar safety profile in advanced breast tumors.