What Is Talazoparib (Talzenna)? FDA Approval, Licensing in Türkiye, and Reimbursement Status
| Active ingredient | Talazoparib |
| Brand name | Talzenna |
| Class | PARP (poly ADP-ribose polymerase) inhibitor — PARP1/2 |
| Category | Targeted antineoplastic agent (oral small molecule) |
| Route of administration | Oral (capsule) |
| Dosing frequency | Daily: 1 dose (1 mg) |
| Approved cancers | gBRCA-mutant, HER2-negative locally advanced/metastatic breast cancer (monotherapy) · HRR gene-mutant metastatic castration-resistant prostate cancer (combined with enzalutamide) |
| FDA-approved | Yes — first approval October 16, 2018 (breast); most recent expansion June 20, 2023 (TALAPRO-2, prostate) |
| Commonly combined medicines | Enzalutamide (mCRPC) |
| Manufacturer | Pfizer Inc. |
| Turkish Ministry of Health license | YES (for breast cancer; licensing of the prostate combination should be confirmed separately) |
| SGK reimbursement | NO — not on the Reimbursable Medicines List |
| Talzenna 1 mg (30 capsules) price | 93,340.22 TL (varies with exchange rates) |
| Half-life | Approximately 90 hours (~3.75 days) |
Talazoparibis a PARP inhibitor that exploits a weakness in the cell's DNA-repair machinery to force cancer cells to destroy themselves—an approach called "synthetic lethality." Initially approved only for BRCA-mutant breast cancer, it also received approval in 2023 in combination with enzalutamide for prostate cancer.
This monograph examines how the medicine works, its FDA approval history, the findings of EMBRACA and TALAPRO-2, its safety profile (particularly myelosuppression and MDS/AML risk), and licensing, price, and SGK reimbursement in Türkiye in detail.
Cells use multiple mechanisms to repair DNA damage. BRCA1/2 mutations already impair the main pathway for repairing DNA double-strand breaks (homologous recombination repair, HRR); these cells become dependent on PARP enzymes to repair smaller single-strand lesions.
Talazoparib blocks the PARP1 and PARP2 enzymes and simultaneously causes PARP protein at the damaged DNA site to become "traps" (PARP trapping). In a BRCA-mutant cell, this leaves no remaining repair pathway—the cell dies from accumulated DNA damage. In healthy, BRCA-proficient cells, the HRR pathway still works, so the effect remains relatively selective.
- Dual mechanism of action: The combination of catalytic PARP inhibition and PARP-DNA trapping makes talazoparib more potent in vitro than some other PARP inhibitors.
- The broader range of HRR genes: Besides BRCA1/2, mutations in other homologous recombination repair genes, such as ATM, ATR, CHEK2, and PALB2, have also been associated with response in prostate cancer.
- Blood-brain barrier: Talazoparib does not cross the blood-brain barrier substantially; neuropsychiatric adverse effects are therefore not expected, but activity against central nervous system metastases may be limited.
| Date | Approval | Evidence |
|---|---|---|
| October 16, 2018 | For deleterious or suspected deleterious germline BRCA-mutant (gBRCAm), HER2-negative locally advanced/metastatic breast cancer, monotherapy approval. | EMBRACA (phase 3) |
| 2019–2022 | The breast cancer indication was approved in more than 70 countries together with the BRACAnalysis CDx companion diagnostic test. | — |
| June 20, 2023 | For HRR gene-mutant metastatic castration-resistant prostate cancer, combination with enzalutamide —the first PARP inhibitor approved in this combination. | TALAPRO-2 (phase 3) |
Although EMBRACA in breast cancer showed a strong progression-free survival (PFS) benefit, the final analysis found no statistically significant difference in overall survival (OS). By contrast, TALAPRO-2 is one of the few studies of a PARP inhibitor + androgen receptor pathway inhibitor combination to demonstrate, in both HRR-mutant and mutation-unselected (all-comer) populations, superior overall survival .
In the all-comer population (n=805), median overall survival in the talazoparib + enzalutamide arm was 45.8 months, versus 37.0 months in the placebo + enzalutamide arm—among the longest median survival times reported in mCRPC to date.
| Study | Patient group | Comparison | Key result |
|---|---|---|---|
| EMBRACA phase 3 · n=431 |
gBRCA-mutant HER2-negative advanced/metastatic breast cancer | Talazoparib vs physician-selected chemotherapy | Median PFS 8.6 versus 5.6 months (HR 0.54; p<0.001). No significant OS difference in the final analysis (19.3 versus 19.5 months; HR 0.848; p=0.17)—subsequent treatments may confound the analysis. Quality-of-life measures favored talazoparib. |
| TALAPRO-2 — all-comers phase 3 · n=805 |
mCRPC, regardless of HRR mutation status, 1st line | Talazoparib + enzalutamide vs placebo + enzalutamide | Median OS 45.8 versus 37.0 months—approximately 20% lower risk of death. rPFS was also significantly prolonged (HR 0.63). |
| TALAPRO-2 — HRR-mutant phase 3 · n=399 |
mCRPC, HRR gene-mutant, 1st line | Talazoparib + enzalutamide vs placebo + enzalutamide | Median rPFS not reached versus 13.8 months (HR 0.45; p<0.0001). Updated analysis showed an OS gain of ~14 months and a 38% reduction in the risk of death; benefit was particularly strong in the BRCA1/2 subgroup (HR 0.50). |
Talazoparib's clinical profile illustrates how the same medicine can produce different outcomes in different tumor types and with different combination partners: strong PFS but limited OS benefit in breast cancer, versus striking superiority in both PFS and OS in prostate cancer. This demonstrates how the combination partner (chemotherapy versus enzalutamide) and disease biology shape outcomes.
The standard dose is 1 mg once daily by mouth, with or without food. Because talazoparib is mainly eliminated through the kidneys, dosing is adjusted to kidney function: no adjustment is needed for mild impairment (CLcr 60–89 mL/min); doses are reduced for moderate (CLcr 30–59) and severe (CLcr 15–29) impairment.
Treatment should not begin before adequate recovery from hematologic toxicity caused by previous chemotherapy. A missed dose should be taken at the next usual time, rather than as soon as it is remembered.
- Moderate kidney impairment (CLcr 30–59 mL/min): reduce the dose to 0.75 mg/day.
- Severe kidney impairment (CLcr 15–29 mL/min): reduce the dose to 0.5 mg/day.
- Strong P-glycoprotein (P-gp) inhibitors (such as amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil) require a dose reduction to 0.75 mg/day during coadministration; return to the previous dose after stopping the inhibitor (after 3-5 half-lives).
- For prolonged hematologic toxicity, interrupt treatment and monitor blood counts weekly; if there is no recovery within 4 weeks, hematology consultation, including bone marrow analysis and cytogenetic examination, is recommended.
Absorption: Oral bioavailability is approximately 54%; peak plasma concentration is usually reached within 1–2 hours. A high-fat/high-calorie meal reduces Cmax by 46% and delays Tmax, but total exposure (AUC) does not change to a clinically meaningful extent.
Distribution: The large distribution volume (~420 L) reflects extensive extravascular tissue distribution. Plasma protein binding is approximately 74%.
Metabolism: Hepatic metabolism is minimal ; interactions involving CYP450 enzymes are therefore not expected.
Elimination: Mainly eliminated through the kidneys as unchanged medicine (urine ~69%, feces ~20%). Mean terminal elimination half-life is 90 hours; steady state is reached in 2–3 weeks.
- Strong P-gp inhibitors (amiodarone, carvedilol, clarithromycin, itraconazole, verapamil, etc.) can increase talazoparib exposure by approximately 45%; avoid coadministration if possible, or reduce the dose if it cannot be avoided.
- Moderate/weak P-gp inhibitors are not expected to have a clinically significant effect; monitoring for signs of toxicity is nevertheless recommended.
- Because talazoparib undergoes minimal hepatic metabolism, CYP450 enzyme inhibitors/inducers are not expected to cause clinically significant interactions.
- Myelosuppressive effects of previous chemotherapy may combine with talazoparib's own bone marrow toxicity in a cumulative manner; full recovery should therefore be awaited before starting treatment.
- As monotherapy (in breast cancer): Fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and reduced appetite are the most frequently reported adverse effects (≥20%).
- Laboratory abnormalities: Decreased hemoglobin, neutrophils/lymphocytes/platelets, raised glucose and liver enzymes (AST, ALP, ALT), and decreased calcium are common.
- Grade ≥3 cytopenias: Anemia was reported in 39%, neutropenia in 21%, and thrombocytopenia in 15%.
- Combined with enzalutamide (in prostate cancer): The most common Grade 3-4 adverse events are anemia (43-49%) and neutropenia (19-20%).
- Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML): A rare but sometimes fatal risk reported with the PARP inhibitor class, including patients receiving talazoparib. Symptoms such as weakness, fever, weight loss, frequent infections, easy bruising/bleeding, and shortness of breath require evaluation; if MDS/AML is confirmed, treatment is permanently discontinued.
- Myelosuppression: Anemia, neutropenia, and/or thrombocytopenia may develop. Complete blood counts are recommended before treatment and monthly ; prolonged cytopenias require treatment interruption and weekly monitoring.
- Embryo-fetal toxicity: Animal studies demonstrated fetal harm. Women of reproductive potential should use effective contraception during treatment; men with female partners should take similar precautions.
- Ovarian reserve: Ovarian follicular atresia was observed in animal studies, suggesting a potential effect on fertility.
Reported resistance mechanisms include, in the BRCA1/2 gene, secondary (reversion) mutations —these can compensate for the original deleterious mutation and partially restore functional HRR repair—and structural changes reducing the PARP protein's ability to bind DNA. Increased activity of drug-efflux pumps such as P-gp may also contribute to resistance by reducing intracellular talazoparib levels. These mechanisms are an active research area for selecting subsequent treatment in patients resistant to PARP inhibitors.
License: Talzenna, is licensed by the Turkish Ministry of Health/TİTCK and can be obtained on prescription from community pharmacies. The licensed indication is monotherapy for germline BRCA1- or BRCA2-mutant, HER2-negative locally advanced or metastatic breast cancer after progression following anthracycline and/or taxane treatment in the neoadjuvant/adjuvant/metastatic setting. Patients previously treated with platinum must not have progressed within 6 months of their last platinum treatment (refractoriness); hormone receptor-positive patients must also have received at least one previous endocrine-based treatment line.
Prostate cancer indication: Although the enzalutamide combination based on TALAPRO-2 is approved in the United States, inclusion of this indication in the Turkish license should be confirmed separately.
Reimbursement: Talazoparib, is not included in SGK's Reimbursable Medicines List, so its cost is not covered. Patients must obtain it from pharmacies entirely at their own expense.
Unlike one-off or intermittently administered chemotherapy/immunotherapy, talazoparib is a tablet/capsule taken until disease progression or unacceptable toxicity, every day . Treatment cost should therefore be calculated over 28-30-day periods rather than "cycles" and assessed throughout treatment cumulatively .
Who is this medicine for? Patients with confirmed germline BRCA1/2 mutations and HER2-negative advanced/metastatic breast cancer (the licensed indication in Türkiye). Without mutation testing, this medicine has no role.
How is it taken? It is a capsule taken orally once daily, with or without food. If a dose is missed, take it at the next usual time, rather than as soon as it is remembered.
What should you watch for? Monthly blood-count monitoring is necessary. Report severe weakness, fever, easy bruising/bleeding, frequent infections, or shortness of breath to your healthcare team immediately—these may indicate bone marrow suppression or the rare condition MDS/AML.
Price and reimbursement in Türkiye: Talzenna is licensed for breast cancer in Türkiye, but it is not covered by SGK. The monthly 1 mg dose (30 capsules) costs 93,340.22 TL. Because the medicine is taken daily for an indefinite period, cumulative costs can become a substantial burden over time; contacting your hospital's social services unit or a healthcare-law attorney is recommended.
Talazoparib illustrates how "synthetic lethality"—selectively targeting cancer cells with a specific genetic defect—can be applied clinically in two tumor types, breast and prostate cancer. Approval of the enzalutamide combination was an important development showing that PARP inhibitors combined with androgen receptor pathway inhibitors may benefit patients regardless of HRR mutation status.
EMBRACA (n=431): In BRCA-mutant breast cancer, PFS was 8.6 versus 5.6 months (HR 0.54), but the final analysis found no significant OS difference. TALAPRO-2 all-comers (n=805): OS 45.8 versus 37.0 months—among the longest survival results reported in mCRPC. TALAPRO-2 HRR-mutant (n=399): rPFS HR 0.45, an OS gain of ~14 months, and a 38% risk reduction; benefit was particularly strong in the BRCA1/2 subgroup.
EMBRACA's failure to demonstrate a significant overall-survival benefit is a reminder that PFS gains do not always translate into OS gains—particularly when numerous later-line treatments confound analysis. Myelosuppression (Grade ≥3 anemia in up to 39%) and rare but serious MDS/AML make regular blood counts essential. Because talazoparib is eliminated through the kidneys, dose adjustment requires care in patients with impaired kidney function. A limitation specific to Türkiye: despite licensing, SGK does not reimburse it.
Before prescribing talazoparib, establishing germline BRCA1/2 status in breast cancer or tumor/germline HRR gene-panel results in prostate cancer through an appropriate, current test is fundamental to the treatment decision. Monthly blood counts and kidney-function-based dose adjustment are the two pillars of safe use. When planning treatment in Türkiye, patients should be told clearly at the outset that this medicine is taken daily for an indefinite period and is not reimbursed by SGK.
What precisely explains benefit in TALAPRO-2 patients without HRR mutations—the biological basis of synergy with enzalutamide? How often does resistance due to BRCA1/2 reversion mutations occur in clinical practice, and how can it be overcome? What is talazoparib's potential role in other solid tumors, such as ovarian or pancreatic cancer? For Türkiye, the most practical questions are when SGK reimbursement will become available and whether the prostate cancer indication will be licensed.
- This document does not provide dose-adjustment advice or recommend any treatment regimen.
- Prices are a snapshot and may change with exchange rates/regulatory price updates.
- SGK does not reimburse this medicine; licensing does not guarantee access or reimbursement.
- EMBRACA did not demonstrate an overall-survival benefit; treatment decisions must account for this nuance.
- The licensing status of the prostate cancer indication in Türkiye should be confirmed separately.
- The decision to use it rests solely with the medical oncology specialist who knows the patient.
- TALZENNA (talazoparib) Prescribing Information, Pfizer Inc. FDA access: accessdata.fda.gov (211651).
- Litton JK, ve ark. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation (EMBRACA). N Engl J Med. 2018;379:753-763.
- Litton JK, ve ark. Talazoparib versus chemotherapy: final overall survival results from EMBRACA. Ann Oncol. 2020;31(11):1526-1535.
- Agarwal N, ve ark. Talazoparib plus enzalutamide in men with mCRPC: final overall survival results from TALAPRO-2. Lancet. 2025.
- Fizazi K, ve ark. First-line talazoparib with enzalutamide in HRR-deficient mCRPC: the phase 3 TALAPRO-2 trial. Nat Med. 2023.
- TALZENNA Kısa Ürün Bilgisi (KÜB), TİTCK, Turkish licensing record.
- NCCN Clinical Practice Guidelines in Oncology: Breast Cancer / Prostate Cancer, current versions.
Editor's note: This monograph is for general information only; it is not medical advice, a diagnosis or treatment recommendation, or promotion of any product. All reported data were verified against primary sources and presented without direct quotation. This document deliberately contains no dose-adjustment advice; dosing information is summarized from FDA prescribing information for general education only, and the treatment decision is solely the treating physician's responsibility. Talazoparib is licensed in Türkiye for breast cancer by the Turkish Ministry of Health/TİTCK, but at the time this article was prepared it was not included in SGK's Reimbursable Medicines List; because prices may change with exchange rates and periodic price decrees, the amounts shown here are a nonbinding snapshot. The Turkish licensing status of the prostate cancer indication combined with enzalutamide could not be verified for this article and requires separate confirmation. EMBRACA did not show a statistically significant overall-survival benefit; this nuance matters when setting treatment expectations. Do not stop or change any medicine without consulting your physician. Consult the physician who knows you for every decision concerning your health.
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