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Talazoparib in Patients With Solid Tumors With BRCA1/2 Mutation: Results From the Targeted Agent and Profiling
Gordan Srkalovic1,2, Michael Rothe3, Pam K Mangat3
1Herbert-Herman Cancer Center, Lansing, MI.
Purpose:
The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported.
Methods:
Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.
Results:
Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected (P < .001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non-small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs).
Conclusion:
Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration-approved.
Insights
Talazoparib showed significant antitumor activity in patients with advanced solid tumors harboring BRCA1/2 mutations. This targeted therapy demonstrated efficacy across various cancer types, offering new hope for patients with specific genetic alterations.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The Targeted Agent and Profiling Utilization Registry Study (TAPUR) is a phase II basket trial.
- It evaluates targeted agents in advanced cancers with known drug-targetable genomic alterations.
- This report focuses on talazoparib in patients with BRCA1/2 mutations.
Purpose of the Study:
- To assess the antitumor activity of talazoparib in patients with advanced solid tumors and BRCA1/2 mutations.
- To determine the disease control (DC) rate, defined as objective response (OR) or stable disease (SD) for at least 16 weeks (SD16+).
Main Methods:
- A cohort of 28 patients with various solid tumors and BRCA1/2 mutations were enrolled.
- Patients had advanced disease, measurable lesions, and ECOG performance status 0-2.
- The primary endpoint was DC, evaluated using a one-sided exact binomial test.
Main Results:
- Talazoparib achieved a DC rate of 57% and an OR rate of 36% in evaluable patients.
- Significant antitumor activity was observed across multiple tumor types, including breast, ovarian, and lung cancers.
- Thirteen patients experienced grade 3-5 adverse events, consistent with talazoparib's known safety profile.
Conclusions:
- Talazoparib demonstrates significant antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations.
- This includes efficacy in cancer types not currently approved for poly ADP-ribose polymerase (PARP) inhibitor treatment by the FDA.
- Talazoparib represents a promising therapeutic option for this patient population.
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