PD-L1 CNA as a biomarker in metastatic breast cancer

Australian researchers believe that PD-L1 may have potential as an indicator of potential response to chemotherapy in women with metastatic breast cancer. That was based on results of a randomized trial, presented at the European Society for Medical Oncology in Lugano, Switzerland.1

In SAFI-2 BREAST IMMUNO, 199 patients with metastatic breast cancer without actionable genetic alterations were randomized to 6 months of standard chemotherapy with durvalumab or maintenance chemotherapy. Of the patients, 83 had triple-negative disease.

For patients to respond to immunotherapy agents that target PD-1 or PD-L1, they tumors must express PD-L1. The aim of the study was to determine the predictive value of copy number alteration (DNA) for the PDL1 gene, which indicates whether the gene number has remained the same, decreased, or increased.

Using metastatic tumor samples from the participants, PDL1 CAN was characterized from array CGH analysis. The authors estimated treatment effect in each subgroup using a Cox Proportional Hazard model.

Results showed that 23.8% of patients had copy gain or amplification of the PDL1 gene. Improvement in overall survival (OS) with durvalumab was limited to this group, with median OS of 9 months (95% confidence interval [CI] 4 to 18) in the chemotherapy arm and not reached in the durvalumab arm (hazard ratio 0.17, 95% CI 0.05 to 0.55).

“This exploratory subgroups analysis of the first randomized trial comparing a PDL1 inhibitor to chemotherapy in the maintenance setting,” the authors said, “shows that PDL1 CNA can be an important predictive marker for PD(L)1 inhibitor efficacy. If their findings are confirmed in a larger trial, they believe it may have important implications for development of immunotherapy in patients with metastatic breast cancer, particularly those with low immunogenicity.