The presence of germline pathogenic variants (gPVs) in DNA repair-related genes is independently associated with worse survival outcomes in patients with advanced breast cancer treated with CDK4/6 inhibitors, according to a real-world study published in JCO Precision Oncology.
Researchers analyzed 217 patients with hormone receptor-positive, HER2-negative advanced breast cancer who were treated with CDK4/6 inhibitors in combination with endocrine therapy. Treatments included palbociclib, ribociclib, or abemaciclib as well as letrozole or fulvestrant.
The study population was stratified into 3 cohorts: patients harboring gPVs in DNA repair-related genes (gBRCA1/2–ATM–CHEK2 mutated), those without these mutations (wild-type), and those who were not tested for these mutations.
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There were 15 patients with gPVs, including BRCA1 (4 patients), BRCA2 (6 patients), ATM (4 patients), and CHEK2 (1 patient). The remaining patients were wild-type (45 patients) or were not tested (157 patients).
The median follow-up was 41.7 months overall. The median progression-free survival (PFS) was shorter in patients with gPVs than in wild-type or non-tested patients — 10.2 months, 15.6 months, and 17.6 months, respectively (P =.002).
Similarly, the median overall survival (OS) was shorter in patients with gPVs than in wild-type patients — 31.4 months and 49.3 months, respectively (P =.006).
On multivariate analysis, mutation status was an independent predictor of PFS and OS. After adjusting for age, performance status, disease site, and prior therapy, wild-type patients had significantly better outcomes than gPV patients. The hazard ratio was 0.463 for PFS (95% CI, 0.241-0.887; P =.020) and 0.314 (95% CI, 0.127-0.777; P =.012) for OS.
“Our results support the necessity of addressing heterogeneity in patients with hormone receptor-positive aBC [advanced breast cancer], given the prevalence of germline homologous recombination-related mutations in this subgroup,” the researchers wrote. “Understanding of clinical outcomes in specific breast cancer populations is urgently needed for a better selection of the treatment strategies.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Bruno L, Ostinelli A, Waisberg F, et al. Cyclin-dependent kinase 4/6 inhibitor outcomes in patients with advanced breast cancer carrying germline pathogenic variants in DNA repair-related genes. JCO Precis Oncol. Published online March 2, 2022. doi:10.1200/PO.21.00140
