medwireNews: The PARP inhibitor talazoparib extends progression-free survival (PFS) and improves quality of life (QoL) compared with standard chemotherapy, show findings from the phase III EMBRACA study of women with advanced breast cancer and a germline BRCA1/2 mutation.
Median PFS was 8.6 months for the 287 patients randomly assigned to receive open-label talazoparib 1 mg/day compared with a median PFS of 5.6 months for the 144 patients who instead received physician’s choice of single-agent therapy with capecitabine, eribulin, gemcitabine, or vinorelbine.
This gave a significant hazard ratio (HR) for disease progression or death of 0.54 in favor of the PARP inhibitor, report Jennifer Litton, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors in The New England Journal of Medicine.
This benefit reflected a significant fivefold higher objective response rate with talazoparib than chemotherapy (62.6 vs 27.2%), while interim analysis after 57% of projected events gave median overall survival times of 22.3 and 19.5 months, respectively, although the HR for death of 0.76 did not reach significance.
Hematologic grade 3 or 4 adverse events occurred in 55% of the talazoparib-treated patients and 38% of controls, most commonly anemia, while nonhematologic events at these grades were reported in 32% and 38%, respectively. Both trial arms had a 9% rate of serious events, with anemia predominant in the talazoparib group and neutropenia most common among those given standard chemotherapy.
“Treatment-associated myelotoxicity was managed by dose modifications or delays,” comment Litton et al, adding that “[i]mprovements in patient-reported outcomes [PROs] indicated that talazoparib had a good side-effect profile.”
PROs for the EMBRACA study have been reported in more detail in the Annals of Oncology by Johannes Ettl, from the Technical University of Munich in Germany, and colleagues.
Baseline scores on the EORTC Quality of Life Questionnaire Core 30 (QLQ-30) and the QLQ-BR23 breast cancer module were comparable in the treatment arms at baseline.
However, talazoparib therapy was associated with a significant improvement in global health status (GHS)/QoL, whereas patients given physician’s choice of chemotherapy experienced a statistically significant decline.
Talazoparib also resulted in a significantly longer delay in the time to clinically meaningful deterioration of GHS/QoL than standard chemotherapy, at 24.3 versus 6.3 months, and a HR of 0.38. And patients using the PARP inhibitor had significant benefits in terms of time to meaningful deterioration of specific symptoms including pain, nausea/vomiting, and fatigue.
“Notably, when comparing between arms, none of the analyses yielded statistically significant PRO results favoring the overall [physician’s choice treatment] arm,” the researchers say.
“Our results further support the positive risk-benefit profile of talazoparib and show that talazoparib does not impose toxicities that interfere with patient QoL.”
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