乌鸦传媒

A novel biomarker identified a large subgroup of metastatic breast cancer patients who benefited from an immune checkpoint inhibitor, according to an exploratory analysis of a prospective clinical trial.

Almost a fourth of patients with no identified actionable mutations had copy number alteration (CNA) in the PD-L1 gene. Patients without PD-L1 CNA had a median progression-free survival (PFS) of 9 months when treated with the PD-L1 inhibitor durvalumab (Imfinzi), whereas median PFS had yet to be reached in patients whose tumors had copy number gain (three or four copies) or amplification (more than four).

If corroborated by additional studies, the results would effectively identify patients with a type of cancer that historically has responded poorly to immunotherapy, Thomas Bachelot, MD, of Leon Berard Center in Lyon, France, .

"This exploratory translational analysis suggested a higher efficacy of durvalumab as maintenance treatment for patients with PD-L1 copy gain or amplification," Bachelot said in a statement. "PD-L1 copy number alteration could be an important predictive marker for PD-L1 inhibitor efficacy. If confirmed in larger series, this could have important implications for the development of immunotherapy in patients with metastatic breast cancer, enabling us to better identify patients that are sensitive to PD-L1 inhibitors than current testing for PD-L1 positivity on immune cells."

Sherene Loi, MD, of the Peter MacCallum Cancer Center in Melbourne, Australia, agreed with the potential implications suggested by Bachelot.

"Immunotherapy has resulted in long durations of disease control, and even cures, with improved quality of life compared with chemotherapy in other cancers," said Loi, who was not involved in the study. "We are hoping this might also be applicable for some breast cancer patients."

"Preexisting immunity, which can be detected by PD-L1 expression, is required for response to PD-1 or PD-L1-targeting immunotherapy agents," she added. "The key question is whether we can identify further patients with metastatic breast cancer that respond to immunotherapy using biomarkers other than just PD-L1 expression."

Another study reported during the virtual meeting added indirectly to the volume of evidence on predictive biomarkers. A randomized trial comparing pembrolizumab (Keytruda) and chemotherapy for patients with metastatic triple-negative breast cancer showed no difference in overall survival (OS), but patients treated with the PD-L1 inhibitor had significantly better quality of life, reported Peter Schmid, MD, of Queen Mary University of London.

Additionally, a subgroup of patients did live longer when they received the PD-1 inhibitor.

Said Loi, "Patients who expressed high levels of PD-L1 protein according to their CPS (combined positive score) had better overall survival with pembrolizumab compared with chemotherapy, and pembrolizumab was far better tolerated than chemotherapy. This underscores the importance of PD-L1 testing in the advanced setting, as well as identifying other biomarkers that can help identify those who do best with pembrolizumab monotherapy given its favorable health-related quality of life impact."

To date only two predictors of immunotherapy efficacy have been identified in metastatic breast cancer: absence of hormone receptors and PD-L1 CPS. However, immunohistochemistry quantification of PD-L1 expression has yet to be standardized, leaving an unmet need for more robust predictors of response, said Bachelot.

Data for the CNA analysis came from the trial, which included 199 patients with metastatic breast cancer that responded to standard chemotherapy. They were randomized 2:1 to maintenance treatment with durvalumab or chemotherapy. Tissue specimens for CNA analysis were available for 126 patients.

Bachelot reported that 23.8% of the specimens revealed either PDL1 copy number gain or amplification. Only patients with CNA (gain or amplification) had a survival benefit with durvalumab. Although the median PFS had not been reached in the CNA subgroup, the data suggested >80% reduction in the hazard for disease progression or death with durvalumab versus chemotherapy maintenance (hazard ratio 0.17, 95% C 0.05-0.55).

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