Quality of life and safety
Patient-reported outcomes continued to favor talazoparib with extended follow-up and were consistent with the initial analysis, Dr. Litton noted.
The updated analysis revealed “a significant improvement in estimated overall change from baseline in the global health quality of life scores for those patients receiving talazoparib, while a significant deterioration was observed in patients receiving chemotherapy,” she said.
The estimated overall change in score was a 2.1-point increase in the talazoparib arm and a 5.7-point decrease in the chemotherapy arm (P = .001). The median time to clinically meaningful deterioration in global health quality of life scores was 26.3 months in the talazoparib arm and 6.7 months in the chemotherapy arm (HR, 0.385).
At the final analysis, the overall safety profile was consistent with that reported previously. Talazoparib was generally well tolerated, and no new safety signals were identified.
Grade 3/4 serious adverse events occurred in 28.3% of patients in the talazoparib arm and 27% of those in the chemotherapy arm. Adverse events led to treatment discontinuation in 7.7% and 9.5% of patients, respectively.
Most grade 3/4 adverse events were hematologic, and most were successfully managed by supportive care, including transfusions and dose modifications, Dr. Litton said.
She noted that one patient in the chemotherapy arm assigned to receive capecitabine had been diagnosed with acute myeloid leukemia at the time of the first analysis. “And now we report an additional case of [acute myeloid leukemia] in a patient who was randomized to the talazoparib arm,” Dr. Litton said.
Jury’s still out
Based on existing data, including from EMBRACA, the jury is still out on whether PARP inhibition is associated with an overall survival benefit in this setting, said invited discussant Susan Domcheck, MD, of the University of Pennsylvania in Philadelphia.
She suggested that could change with ongoing efforts to identify biomarkers for treatment response and new approaches to treatment, such as earlier lines of therapy and combinations.
“At this time, germline BRCA 1 and 2 pathogenic variants are the best predictor of PARP inhibitor sensitivity in breast cancer,” Dr. Domcheck said. “Not all the tumors are sensitive, but this is true of [estrogen receptor–positive] breast cancer and hormonal therapy, and HER2-positive breast cancer as well.”
Studies investigating approaches to improve survival are “incredibly important, because the progression-free survival is not as long as we would like it to be and there’s not an overwhelming overall survival benefit, for sure,” she said.
The EMBRACA trial was funded by Medivation (Pfizer). Dr. Litton and colleagues disclosed numerous relationships with pharmaceutical companies and other organizations. Dr. Domcheck disclosed relationships with AstraZeneca, Clovis, and Bristol Myers Squibb.
SOURCE: Litton J et al., AACR 20, Abstract CT071.