The impact of previous therapy on overall-survival in registration clinical trials for 1st line metastatic breast cancer a systemic review.

Aim: To explore the impact of previous treatment on the efficacy of investigational new drugs in registration trials for 1st line metastatic breast cancer (MBC).

Methods: Thirteen US Food and Drug Administration (FDA) approved indications for 1st line MBC between 1/2000-12/2023 were identified and their supporting publications were searched in the ClinicalTrials.gov and Google Scholar. Where available, hazard ratios (HRs) and 95 % confidence intervals (CI) for overall-survival (OS) were pooled into meta-analysis and the difference in the magnitude of OS benefit between treatment naïve and previously treated patients was analyzed.

Results: There was no difference in the magnitude of OS benefit between treatment-naïve and previously treated patients (HR=0.72 versus 0.80,p for difference=0.25). In indications for triple-negative BC, treatment-naïve patients had higher magnitude of OS benefit compared to previously treated patients (HR=0.53 versus 0.81,p=0.03). In indications for luminal disease, the magnitude of benefit was comparable between the subgroups.

Conclusions: In trials supporting 1st line therapy for TNBC the magnitude of benefit is significantly higher in treatment naïve compared to previously treated patients. Our findings may represent a previously unrecognized bias, potentially over-estimating the benefit of triple-negative BC new drugs.