Germline BRCA mutations and other HR genes may offer biomarkers for response to this treatment.
Extended follow-up from a randomized trial confirmed that a regimen of cisplatin plus gemcitabine (GP) offers superior efficacy over paclitaxel plus gemcitabine (GT) as first-line treatment of patients with triple-negative breast cancer (TNBC). Germline BRCA mutations and other homologous recombination (HR) genes may offer biomarkers for response to this treatment.
“TNBC has the worst prognosis among all subtypes of breast cancer, featuring genomic instability due to abnormal DNA repair systems caused by mutations in BRCA1/2 and/or other genes involved in HR repair mechanisms,” wrote study authors led by Xichun Hu, MD, of Fudan University Shanghai Cancer Center in China. The new analysis was published in Annals of Oncology.
The updated analysis included a total of 212 patients with TNBC. Over a median follow-up period of 54.73 months, the median progression-free survival (PFS) was 7.73 months with GP and 6.07 months with GT (P = .005). There were no statistically significant differences between the groups with regard to overall survival.
Patients with at least one pathogenic or likely-pathogenic mutation in any of 28 HR genes were classified as HR-deficient (HRD). The HRD patients had significantly longer overall survival, at 24.07 months, compared with 18.03 months in non-HRD patients (P = .006).
There was a significant interaction seen between HR status and treatment for both PFS and overall response rate (ORR). HR deficiency correlated with a median PFS of 10.37 months, compared with 4.30 months, and the difference in ORR was 71.9% vs 38.7%. No significant interaction was seen between germline BRCA1/2 status and treatment with regard to PFS.
Patients with germline BRCA1/2 mutations had a numerically higher ORR with GP than with GT (83.3% vs 37.5%; P = .086). Similarly, they had a numerically longer PFS with GP than with GT, at 8.90 months vs 3.20 months (P = .459). There was no evidence of difference in efficacy in those with wild-type BRCA1/2.
Programmed death ligand 1 (PD-L1) expression was assessed in just under half the cohort (48.3%), and there was no significant interaction seen between PD-L1 status and treatment.
“We identified germline BRCA1/2 mutations and HRD as possible biomarkers for better performance of platinum doublet, and we recommend routine germline BRCA1/2 detection,” the authors concluded. They developed a composite risk model using these markers, but noted that validation in larger clinical trials is still needed.