Outcomes of patients with HER2-negative metastatic breast cancer after platinum- and non-platinum-based first-line chemotherapy among patients with and without pathogenic germline BRCA1/2 mutations

Background The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (g BRCA1/2 m and g BRCA1/2 wt, respectively). Methods We selected from the French national real-world multicentre ESME cohort (2008–2016) all patients with HER2-negative MBC with known g BRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients’ g BRCA1/2 status and tumour subtype. Results Patients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in g BRCA1/2 m carriers ( N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4–0.73, P < 0.001, and HR 0.70, 95% CI 0.49–0.99, P = 0.047, respectively). Conversely, outcomes were similar in g BRCA1/2 wt patients ( N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results. Conclusions In this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with g BRCA1/2 m, but not in those with g BRCA1/2 wt. These results emphasise the need of early g BRCA1/2 testing in patients with MBC. Clinical trial number NCT03275311.