PFS Boost With Talazoparib In BRCA Mutation-Positive Patients With Advanced Breast Cancer

Phase III trial results support the use of talazoparib in locally advanced or metastatic breast cancer patients with a BRCA1/2 mutation

medwireNews: Treatment with the PARP inhibitor talazoparib leads to significantly better progression-free survival (PFS) than standard chemotherapy in previously treated patients with advanced breast cancer and a germline BRCA1/2 mutation, report the EMBRACA investigators.

In the phase III trial, the risk of progression or death was a significant 46% lower for the 287 participants with locally advanced or metastatic disease who were randomly assigned to receive talazoparib 1 mg/day than for their 144 counterparts who received physician’s choice of standard single-agent chemotherapy (capecitabine , eribulin , gemcitabine or vinorelbine ). The median PFS durations were 8.6 and 5.6 months, respectively.

As reported in The New England Journal of Medicine, the objective response rate was also significantly higher with talazoparib than chemotherapy, at 62.6% versus 27.2%.

And although the overall survival data are not mature, the interim results are “promising”, with a nonsignificant hazard ratio for death of 0.76 favouring talazoparib, say Jennifer Litton, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

They also stress “the qualitative and quantitative differences in safety between talazoparib and standard chemotherapy” in this patient population.

“Most grade 3–4 toxic effects associated with the use of talazoparib were hematologic laboratory abnormalities, were not associated with substantial clinical sequelae, and did not result in drug discontinuation”, the team writes.

Specifically, haematological adverse events of grade 3 or 4 occurred in 55% of talazoparib-treated patients and 38% of those given chemotherapy, while nonhaematological grade 3 toxicities were observed in 32% and 38% of participants, respectively.

The corresponding rates of discontinuation due to adverse events were 5.9% and 8.7%, and one death in both the talazoparib and chemotherapy groups was attributed to the study drug, a case of veno-occlusive disease and sepsis, respectively.

Talazoparib was also associated with better patient-reported outcomes than standard chemotherapy, with significant overall improvements and delays in the onset of clinically meaningful deterioration as assessed by both the core EORTC Quality of Life Questionnaire (QLQ-C30) and the breast cancer-specific scale (QLQ-BR23). For instance, the average EORTC QLQ-C30 score increased by 3.0 points from baseline in the talazoparib study arm and decreased by 5.4 points in the chemotherapy arm, a significant difference.

Reference

Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation . N Engl J Med; Advance online publication 15 August 2018. doi:10.1056/NEJMoa1802905

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