Pfizer Korea said that the Ministry of Food and Drug Safety has approved Talzenna, its BRCA (Breast Cancer Susceptibility Gene) mutation breast cancer targeted therapy....treatment as monotherapy for germline BRCA (gBRCA) mutations and HER2 (human epithelial cell growth factor receptor 2) negative locally advanced or metastatic breast cancer patients have previously had chemotherapy.

Talzenna is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer.

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer.

Recommendations...For BRCA1/2 mutation carriers with metastatic human epidermal growth factor receptor 2 (HER2) –negative breast cancer, olaparib or talazoparib should be offered as an alternative to chemotherapy in the first- to third-line settings.

Recommendations...Patients with HER2-negative MBC and germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2 should be offered treatment with a PARP inhibitor (olaparib or talazoparib) independent of HR status...

Biomarkers associated with FDA-approved therapies...While olaparib and talazoparib are FDA indicated in HER2-negative disease, the panel supports use in any breast cancer subtype associated with a germline BRCA1 or BRCA2 mutation.

Patients with HER2-negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician's choice)….In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy.

...If germline BRCA 1 or 2 (1/2) mutation positive, should be among the 5 patients (in Stage I) or 9 patients (in Stage II) with germline BRCA 1/2 mutation positive....

...Patients who can receive germline BRCA1/2 mutation test or patients with previously known germline BRCA1/2 mutation status....

...- Patients with only a VUS (Variant of Unknown Significance), or non-functional BRCA mutation, without a deleterious somatic BRCA 1 or 2 mutation will...

...- Germline BRCA 1/2 Mutation Positive...

... Age ≥18 years WHO performance status 0-2 Advanced breast cancer Patients must have (had) a high grade (Bloom & Richardson grade 3) ER positive (>10%) and HER2 negative primary breast cancer or a triple negative (ER/PR<10%, HER2 negative) primary breast cancer or breast cancer and a BRCA1 and/or BRCA2 germline mutation The site of the metastatic lesion (or primary tumor in case it is still in situ) should be easily amendable for biopsy. ...

...- gBRCA1/2 mutation(s)...

...- Identified deleterious mutation in BRCA 1 or 2 genes (this does...

We analyzed data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA 1 or BRCA 2 or in the Homologous Recombination Repair genes, treated with olaparib or talazoparib in daily clinical practice...The rwORR was 47.0%, and the median rwPFS1 was 7.77 months (CI95% 5.67-14.7)...

Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy...median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%.

This phase 1, open-label, multicenter study evaluated talazoparib monotherapy in Japanese patients with germline BRCA mutations and HER2-negative locally advanced or metastatic breast cancer...Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1)....In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs.

This phase 2, non-randomized, single-arm, open-label study (NCT03499353) evaluated the efficacy and safety of TALA in the neoadjuvant setting for pts with early gBRCA1/2-mutated HER2− BC....TALA monotherapy in the neoadjuvant setting was active and showed pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens...

The biomarker analysis population was all pts treated with TALA for whom biomarker results are available...Of 52 evaluable tumor samples from 61 treated pts, 39 (75%) and 13 (25%) pts exhibited BRCA1 and BRCA2 mutations, respectively...Tumor BRCA mutations were evident in nearly all pts in the biomarker analysis population...These results support the central role of BRCA mutations in tumor pathobiology in this indication.

To compare the efficacy, safety, and acceptability of single-agent poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer....Compared with talazoparib, olaparib was not associated with improved PFS (HR = 1.08, 95% CrI = 0.34-3.45) or OS (HR = 1.18, 95% CrI = 0.61-2.31). Compared with talazoparib, olaparib was associated with non-significantly improved ORR (OR = 0.83, 95% CrI = 0.05-12.64).

...neoadjuvant talazoparib, administered as a single-agent in patients with HER2-negative breast cancer and germline BRCA1/2 mutation, achieved an impressive pathological complete response rate of nearly 50%.

16 patients were gBRCA1 positive and 4 patients were gBRCA2 positive... RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%.