Talazoparib may benefit patients with PALB2-mutated breast cancer
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Talazoparib appeared effective among certain patients with advanced, PALB2-mutated breast cancer, according to study results published in Nature Cancer.
Additionally, talazoparib (Talzenna, Pfizer), a poly(ADP)-ribose polymerase (PARP) inhibitor, appeared safe, with treatment-associated adverse events similar to those previously reported with the agent, researchers concluded.
Background and methods
“We know that PARP inhibitors are effective for BRCA1/BRCA2-associated cancers and that both appear to be DNA repair factors,” Joshua J. Gruber, MD, PhD, assistant professor of internal medicine at UT Southwestern Medical Center, told Healio. “We also know there are a host of other DNA repair genes that can be mutated in breast cancers. Therefore, we wanted to test whether any additional DNA repair factors were associated with treatment response to talazoparib.”
The open-label, phase 2, Talazoparib Beyond BRCA trial evaluated 1 mg daily talazoparib in 20 patients (median age, 53.9 years; 75% women), including 13 pretreated advanced HER2-negative breast cancer and seven with other tumor types with mutations in homologous recombination pathway genes other than BRCA1/BRCA2.
All patients received a median two prior lines of treatment for advanced-stage disease.
Median treatment duration was 23.8 weeks.
Findings
Results showed four patients (20%) achieved a RECIST partial response and three achieved stable disease of 6 months or longer. Median OS was 5.6 months.
All patients with germline mutations in PALB2 experienced treatment-associated tumor regression and median PFS of 6.9 months.
Researchers additionally observed an association between tumor or plasma circulating tumor DNA homologous recombination deficiency scores and treatment outcomes, which were increased in all PALB2 tumors.
Treatment-associated adverse events appeared manageable — 55% of patients experienced a hematologic adverse event of any grade and 30% experienced a grade 3 hematologic adverse event. Moreover, five patients required a dose reduction due to hematologic toxicity, three patients required red blood cell transfusions during treatment, and two patients required platelet transfusions.
Implications
“Patients with metastatic breast cancer should be offered genetic testing to determine if they have a PALB2 mutation,” Gruber told Healio. “This is commonly evaluated on most next-generation sequencing panels available on the market. If a patient tests positive for a PALB2 mutation, they should be offered a PARP inhibitor, including either talazoparib or olaparib [Lynparza; AstraZeneca, Merck].”
Researchers are now examining additional biomarkers of response to talazoparib.
“We are also expanding our study to a larger patient population to confirm these results and make a case for FDA approval for patients with PALB2-associated breast cancers,” he said.
References:
- Breast cancer drug benefits broader group of patients, trial shows (press release). Available at: www.utsouthwestern.edu/newsroom/articles/year-2022/october-breast-cancer-drug.html. Published Oct. 26, 2022. Accessed Dec. 28, 2022.
- Gruber JJ, et al. Nat Cancer. 2022;doi:10.1038/s43018-022-00439-1.
For more information:
Joshua J. Gruber, MD, PhD, can be reached at joshua.gruber@utsouthwestern.edu.
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