In recent years, the term PARP has come up frequently in the field of oncology, and PARP inhibitors, also known as poly(adenosine diphosphate ribose) polymerase inhibitors, have become a hot topic in the field of breast and ovarian cancer, attracting a lot of attention.
Talazoparib is a member of the PARP inhibitors, and in advanced HER2-negative breast cancer with a BRCA mutation, Talazoparib may further control disease progression compared to chemotherapy. The drug is not yet available domestically or internationally, but its favorable efficacy is noteworthy.
The “mystery” of PARP inhibitors against cancer
Talazoparib is a PARP inhibitor that works primarily in patients with BRCA mutations. The underlying reason is that tumor cells with BRCA mutations have insufficient capacity for DNA damage repair, and tumor cells tend to rely on PARP for repair when they are damaged.
When the PARP inhibitor is used, the DNA repair function of tumor cells is disrupted, and its ability to kill BRCA mutated tumor cells while having less impact on normal cells.
BRCA mutant breast cancer: Talazoparib works in both late and early stages
The EMBRACA study is a phase III clinical study that enrolled 431 patients with HER2-negative advanced breast cancer, all carrying BRCA mutations.
The study found that compared with single-agent chemotherapy, Talazoparib prolonged progression-free survival by 3 months ( 5.6 months, 8.6 months, respectively), with a 46% reduction in the risk of disease progression, and a substantial improvement in objective remission rates compared with single-agent chemotherapy 35.4% ( 27.2%, 62.6%, respectively).Talazoparib has the momentum to increase patient survival time, but it is not fully validated at this time.
In further detailed analysis, Talazoparib improved patients’ quality of life by 62%, and clinical benefit was improved by 53% and 68% in patients with hormone receptor-positive and brain metastases, respectively.
For safety, Talazoparib and chemotherapy were similar in terms of the incidence of grade 3 to 4 serious adverse reactions ( 26%, 25%, respectively), with higher hematologic adverse reactions (55%, 39%). hematologic adverse reactions to Talazoparib treatment were primarily anemia, whereas chemotherapy was primarily neutropenia. granulocytopenia.
In this study, Talazoparib demonstrated significant advantages over chemotherapy in slowing tumor progression, improving quality of life, and tolerable adverse effects.
Neoadjuvant treatment of breast cancer before surgery has the opportunity to reduce tumor size and allow some patients who cannot be breast conserved to have breast conservation or allow some patients who cannot have surgery to have surgery.
Do patients with HER2-negative breast cancer who have a BRCA mutation have a chance to benefit from PARP inhibitors?
Investigators used Talazoparib for preoperative neoadjuvant treatment of breast cancer. Thirteen patients were selected for the study and given 2 months of Talazoparib treatment before surgery, sequential anthracycline, paclitaxel-based chemotherapy ± carboplatin.
The results showed that all patients experienced varying degrees of tumor shrinkage. No serious adverse reactions occurred during treatment, and only 1 person had their dose reduced due to moderate side effects. The most common adverse reactions included neutropenia, anemia, thrombocytopenia, nausea, dizziness, and fatigue.
Considering Talazoparib’s demonstrated antitumor efficacy and better safety profile as a preoperative agent, investigators will continue to explore its potential in neoadjuvant therapy.
The quest is still on
Talazoparib monotherapy has achieved good results in the treatment of BRCA mutant breast cancer, and it is worth exploring further whether combination therapies can achieve a 1+1 > 2 effect. For example, studies related to combining carboplatin and paclitaxel, and inhibitors of HSP90, or heat shock protein, which is an antitumor therapeutic target, are underway.
Summary
- Talazoparib reduced the risk of disease progression in BRCA mutant, HER2 negative advanced breast cancer by 46% compared with single-agent chemotherapy.
- For HER2 negative/BRCA mutation-positive breast cancer, preoperative neoadjuvant therapy with the PARP inhibitor Talazoparib can reduce tumor size by more than 80% in some patients.
Of the currently marketed PARA inhibitors, only Olaparib is approved for breast cancer, and the drug is marketed in China for ovarian cancer treatment.Talazoparib has shown efficacy results that give us reason to expect its expanded indications for breast cancer.