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

Abstract

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.