breast cancer BRCA (2)

TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes

In the December 20, 2020 edition of Journal of Clinical Oncology, Nadine M. Tung, Reported on the results of the TBCRC trial.

PURPOSE

Olaparib was the first poly (ADP-ribose) polymerase (PARP) inhibitor approved in the United States.  After its approval in ovarian cancer, but then found approval of metastatic HER-2/neu negative BRCA 1 and 2 mutated breast cancer.  The investigators wanted to study the efficacy of olaparib in patients who have metastatic breast cancer with underlying somatic BRCA1 or BRCA2 mutations or germline/somatic mutations in homologous recombination (HR)–related genes besides BRCA1/2.

METHODS

In this investigator initiated, phase 2 clinical trial, patients with MBC and germline mutations in non-BRCA1/2 HR-related genes (cohort 1) or somatic mutations in these genes or BRCA1/2 (cohort 2), without any prior exposure to PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens were enrolled. Olaparib was dosed to 300 mg orally twice a day until progression. A two-stage single-arm design was used. The primary endpoint was ORR. Secondary endpoints included CBR and PFS.

RESULTS

54 patients were enrolled.  76 percent had estrogen receptor–positive HER2-negative disease, 87 percent had mutations in PALB2, sBRCA1/2, ATM, or CHEK2. In cohort 1, the ORR was 33% (90% CI, 19% – 51%) and in cohort 2, 31% (90% CI, 15% to -51 %). Confirmed responses were seen only with germline PALB2 (ORR, 82%) and somatic BRCA1/2 (ORR, 50%) mutations. The median PFS was 13.3 months (90% CI, 12 months to not available/computable [NA]) for germline PALB2 and 6.3 months (90% CI, 4.4 months to NA) for somatic BRCA1/2 mutation carriers.  Patients with ATM or CHEK2 mutations alone showed no responses.

The authors concluded “ PARP inhibition is an effective treatment for patients with MBC and gPALB2 or sBRCA1/2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC.”

Reference:

TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes

https://ascopubs.org/doi/full/10.1200/JCO.20.02151

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