Talzenna

Treatment with Talzenna should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Patient selection Breast cancer Patients should be selected for the treatment of breast cancer with Talzenna based on the presence of deleterious or suspected deleterious germline BRCA mutations determined by an experienced laboratory using a validated test method.

Genetic counselling for patients with BRCA mutations should be performed according to local regulations, as applicable. Prostate cancer There is no requirement for tumour mutation testing for selection of patients with mCRPC for treatment with Talzenna.

Posology Talzenna monotherapy (breast cancer) The recommended dose is 1 mg talazoparib once daily. Patients should be treated until disease progression or unacceptable toxicity occurs. 5 mg talazoparib in combination with 160 mg enzalutamide once daily.

Patients should be treated until disease progression or unacceptable toxicity occurs. Medical castration with luteinising hormone releasing hormone (LHRH) analogue should be continued during treatment in patients not surgically castrated.

4 Please refer to the full enzalutamide product information for the recommended posology. Missing dose If the patient vomits or misses a dose of Talzenna, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.

Dose adjustments To manage adverse drug reactions, interruption of treatment or dose reduction based on severity and clinical presentation should be considered (see Table 1). Recommended dose reduction levels for talazoparib monotherapy (breast cancer) and for talazoparib when used in combination with enzalutamide (prostate cancer) are indicated in Table 2 and Table 3, respectively.

4). Table 1. Dose adjustments for adverse reactions Withhold Talzenna until levels resolve to Resume Talzenna Haemoglobin < 8 g/dL ≥ 9 g/dL Resume Talzenna at next lower dose Platelet count < 50 000/μL ≥ 75 000/μL Neutrophil count < 1 000/μL ≥ 1 500/μL Non-haematologic adverse reaction Grade 3 or Grade 4 ≤ Grade 1 Consider resuming Talzenna at next lower dose or discontinue Table 2.

25 mg once daily Table 3. 1 mg once daily Please refer to the full enzalutamide product information for dose adjustment for adverse reactions associated with enzalutamide. 1 mg capsule is to support dose modifications and it is not interchangeable with other strengths.

5 mg in combination with enzalutamide 160 mg in the TALAPRO-2 study. 1%). 1%). 7% of patients receiving Talzenna 1 mg monotherapy. 9%). 6%). 2). 1% of patients with mCRPC receiving Talzenna in combination with enzalutamide; the most common was anaemia (44%).

2%). 3%). 14). Tabulated list of adverse reactions Table 4 summarises adverse reactions based on pooled dataset listed by system organ class, and frequency category. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1 000 to < 1/100).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 4. 9) N/A 10 Table 4. 3) N/A Abbreviations: n=number of patients; N/A=not applicable. * Grade 5 adverse reactions were reported. a.

4. b. Includes preferred terms of thrombocytopenia and platelet count decreased. c. Includes preferred terms of anaemia, haematocrit decreased, haemoglobin decreased and red blood cell count decreased. d. Includes preferred terms of neutropenia and neutrophil count decreased.

e. Includes preferred terms of leukopenia and white blood cell count decreased. f. Includes preferred terms of lymphocyte count decreased and lymphopenia. g Includes preferred terms of pulmonary embolism, deep vein thrombosis, embolism venous and venous thrombosis.

4. h. Includes preferred terms of abdominal pain, abdominal pain upper, abdominal discomfort and abdominal pain lower. i. Includes preferred terms of fatigue and asthenia. Description of selected adverse reactions Myelosuppression Myelosuppression-related adverse reactions of anaemia, neutropenia and thrombocytopenia were very commonly reported in patients treated with talazoparib.

0%. No deaths were reported due to myelosuppression-related adverse reactions. 6% of patients. 8%. 5% of patients required blood transfusions. 2%. 5% of patients. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

8). Talazoparib should not be started until patients have recovered from haematological toxicity caused by previous therapy (≤ Grade 1). Precautions should be taken to routinely monitor haematology parameters and signs and symptoms associated with anaemia, leukopenia/neutropenia, and/or thrombocytopenia in patients receiving talazoparib.

2). Supportive care with or without blood and/or platelet transfusions and/or administration of colony stimulating factors may be used as appropriate. Myelodysplastic syndrome/Acute myeloid leukaemia Myelodysplastic syndrome/Acute Myeloid Leukaemia (MDS/AML) have been reported in patients who received poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, including talazoparib.

8). Potential contributing factors for the development of MDS/AML include previous platinum-containing chemotherapy, other DNA damaging agents or radiotherapy. Complete blood counts should be obtained at baseline and monitored monthly for signs of haematologic toxicity during treatment.

If MDS/AML is confirmed, talazoparib should be discontinued. Venous thromboembolic events In patients with mCRPC a higher incidence of venous thromboembolic events was observed with Talzenna in combination with enzalutamide compared with enzalutamide alone.

8). 3), and may cause foetal harm when administered to a pregnant woman. 6). Women of childbearing potential should not become pregnant while receiving Talzenna and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment.

A highly effective method of contraception is required for female patients during treatment with Talzenna, and for at least 7 months after completing therapy. 6). Male patients with female partners of reproductive potential or pregnant partners should be advised to use effective contraception (even after vasectomy), during treatment with Talzenna and for at least 4 months after the final dose.

1. 6). 6