Dr. Domchek on Results of the MEDIOLA Trial in BRCA-Mutated Metastatic Breast Cancer

Susan Domchek, MD
Published: Thursday, Oct 31, 2019



Susan Domchek, MD, director, MacDonald Women’s Cancer Risk Evaluation Center, executive director, the Basser Center for BRCA, and Basser Professor in Oncology, at Penn Medicine, discusses the results of the phase II 63.36636 trial in germline BRCA-mutated metastatic breast cancer.

Prior results showed a 12-week disease-control rate (DCR) of 80% with the combination of durvalumab (Imfinzi) and olaparib (Lynparza) in 30 patients with germline BRCA-mutated metastatic breast cancer. At 28 weeks, the DCR was 50%. Data presented at the 2019 ESMO Congress demonstrated an objective response rate of 63.3% (95% CI, 43.9-80.1) in the full analysis set. Similar responses were observed in the triple-negative and hormone receptor–positive subgroups, says Domchek.

Investigators also evaluated PD-L1, CD3, and CD8 expression as potential predictors of duration of response and overall survival; however, none of these markers showed a direct correlation, says Domchek. In terms of mechanisms of resistance, 3 patients who progressed early were found to have resistance mutations to olaparib—specifically, a reversion mutation, the absence of allele-specific loss of heterozygosity, and a TP53BP1 mutation.
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Susan Domchek, MD, director, MacDonald Women’s Cancer Risk Evaluation Center, executive director, the Basser Center for BRCA, and Basser Professor in Oncology, at Penn Medicine, discusses the results of the phase II 63.36636 trial in germline BRCA-mutated metastatic breast cancer.

Prior results showed a 12-week disease-control rate (DCR) of 80% with the combination of durvalumab (Imfinzi) and olaparib (Lynparza) in 30 patients with germline BRCA-mutated metastatic breast cancer. At 28 weeks, the DCR was 50%. Data presented at the 2019 ESMO Congress demonstrated an objective response rate of 63.3% (95% CI, 43.9-80.1) in the full analysis set. Similar responses were observed in the triple-negative and hormone receptor–positive subgroups, says Domchek.

Investigators also evaluated PD-L1, CD3, and CD8 expression as potential predictors of duration of response and overall survival; however, none of these markers showed a direct correlation, says Domchek. In terms of mechanisms of resistance, 3 patients who progressed early were found to have resistance mutations to olaparib—specifically, a reversion mutation, the absence of allele-specific loss of heterozygosity, and a TP53BP1 mutation.

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