By Matthew Cotter, PhD, Vice President, Global Medical Affairs, Prostate Cancer, Pfizer Oncology
Sponsored by Pfizer Inc.
Prostate cancer is the second most common cancer in American men, following skin cancer.1 While prostate cancer symptoms can be different for everyone, most patients do not experience any symptoms leading up to a diagnosis.2 Given the disease’s prevalence, ongoing scientific research is needed to better understand prostate cancer and identify treatment options to help address unmet needs of patients.
These unmet needs are particularly prevalent in advanced prostate cancer, which is prostate cancer that has spread to another part of the body.3 One type of advanced disease is known as metastatic castration-resistant prostate cancer (mCRPC).4 mCRPC is when cancer growth is no longer inhibited by low testosterone levels and the cancer has spread to other parts of the body, making it more difficult to treat.3 Approximately 10% to 20% of patients will develop mCRPC within 5 to 7 years of initial prostate cancer diagnosis.4
Understanding the Role of Genetic Mutations in mCRPC
Genomic testing, along with other prostate cancer screening tests, can help patients and their care teams better understand their prognosis, risk of advanced disease and whether there are appropriate medications that may help treat their disease. Certain guidelines recommend these tests be used in metastatic prostate cancer.5,6 For example, somatic tumor testing for alterations in homologous recombination DNA repair genes, such as ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C, is recommended for patients with progression to metastatic prostate cancer.7 About 25% of mCRPC patients have a homologous recombination repair (HRR) mutation.6,7,8 HRR mutations can lead to an earlier onset of disease, more aggressive tumors, higher recurrence rate, and poor prognosis.7,9 By having a better understanding of an individual’s disease, physicians can determine treatment options based on these specific gene mutations.10
At Pfizer, we’re helping to bring forward treatment options in advanced prostate cancer. In June 2023, Pfizer was proud to be able to start offering a therapy for U.S. patients diagnosed with mCRPC and certain HRR mutations. TALZENNA® (talazoparib) was approved by the U.S. Food and Drug Administration (FDA) in combination with XTANDI® (enzalutamide) for the treatment of adult patients with HRR gene-mutated mCRPC.10 The approval is based on results from the Phase 3 TALAPRO-2 trial, a randomized, double-blind, placebo-controlled, multinational study, which demonstrated a 55% reduction in the risk of disease progression or death in patients with mCRPC with prospectively identified HRR gene mutations (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) treated with TALZENNA plus XTANDI versus placebo plus XTANDI (HR 0.45; 95% CI, 0.33–0.61; p<0.0001). The study included two patient cohorts: all-comers (n=805) and those with and without gene mutations (HRRm; n=399). The OS data were not mature at the time of the radiographic progression-free survival (rPFS) analysis (24% of patients had died). Serious adverse reactions of TALZENNA in combination with XTANDI occurred in 30% of patients. Serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%).
Important Safety Information
- Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): MDS/AML occurred in patients exposed to TALZENNA, and some cases were fatal. Monitor patients for hematological toxicity and discontinue if MDS/AML is confirmed.
- Myelosuppression: TALZENNA may affect hematopoiesis and can cause anemia, neutropenia, and/or thrombocytopenia.
For additional information about these Warnings and Precautions, and Important Safety Information, including TALAPRO-2 most common adverse reactions, please see the TALZENNA® (talazoparib) Important Safety Information here. The full U.S. Prescribing Information and Patient Information is available here.
Creating Impact Beyond the Lab
At Pfizer, we recognize the importance of identifying new ways to treat advanced forms of prostate cancer. With more than 15 years of experience in genitourinary cancers, we understand that ongoing research to transform the treatment landscape and offering options for patients where there remains a great unmet need requires a multifaceted approach in collaboration with industry, advocacy, and academia. Along with our commitment to effectively address global health inequities that impact care, we believe we can change expectations for what is possible within the treatment landscape of advanced prostate cancer.
Pfizer’s This Is Living With Cancer™ is a comprehensive program from Pfizer Oncology to support people in their cancer journey, with a growing focus on underserved communities who experience challenges in access to care, such as: people living with cancer over the age of 65, racial and ethnic minorities, those of lower income or individuals who live in rural areas who may not have equal access to resources. It offers valuable information for managing a prostate cancer diagnosis with information on clinical trials, accessing quality care, and working with your doctor.
Whether making scientific discoveries in the lab or working to ensure more equitable patient access to health information, treatment, and support, Pfizer remains driven to improve the care of patients living with advanced prostate cancer.
TALZENNA® (talazoparib) Indication in the U.S.
- TALZENNA is indicated in combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
TALZENNA® (talazoparib) Important Safety Information
WARNINGS and PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide. The durations of TALZENNA treatment in these five patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years, respectively. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy.
Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.
Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia have been reported in patients treated with TALZENNA. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 45%, 18%, and 8% of patients receiving TALZENNA and enzalutamide. Overall, 39% of patients (199/511) required a red blood cell transfusion, including 22% (111/511) who required multiple transfusions. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 7%, 3%, and 0.4% of patients.
Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics.
Embryo-Fetal Toxicity TALZENNA can cause fetal harm when administered to pregnant women. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for 4 months after receiving the last dose.
ADVERSE REACTIONS
Serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%). Fatal adverse reactions occurred in 1.5% of patients, including pneumonia, COVID infection, and sepsis (1 patient each).
The most common adverse reactions (≥ 10%, all Grades), including laboratory abnormalities, for patients in the TALAPRO-2 study who received TALZENNA in combination with enzalutamide vs patients receiving placebo with enzalutamide were hemoglobin decreased (79% vs 34%), neutrophils decreased (60% vs 18%), lymphocytes decreased (58% vs 36%), fatigue (49% vs 40%), platelets decreased (45% vs 8%), calcium decreased (25% vs 11%), nausea (21% vs 17%), decreased appetite (20% vs 14%), sodium decreased (22% vs 20%), phosphate decreased (17% vs 13%), fractures (14% vs 10%), magnesium decreased (14% vs 12%), dizziness (13% vs 9%), bilirubin increased (11% vs 7%), potassium decreased (11% vs 7%), and dysgeusia (10% vs 4.5%).
Clinically relevant adverse reactions in <10% of patients who received TALZENNA with enzalutamide included abdominal pain (9%), vomiting (9%), alopecia (7%), dyspepsia (4%), venous thromboembolism (3%) and stomatitis (2%).
Based on animal studies, TALZENNA may impair fertility in males of reproductive potential.
DRUG INTERACTIONS
Coadministration with P-gp inhibitors The effect of coadministration of P-gp inhibitors on talazoparib exposure when TALZENNA is taken in combination with enzalutamide has not been studied. Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a P-gp inhibitor.
Coadministration with BCRP inhibitors Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a BCRP inhibitor. Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure, which may increase the risk of adverse reactions.
USE IN SPECIFIC POPULATIONS
Renal Impairment The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 - 59 mL/min) is 0.35 mg taken orally once daily in combination with enzalutamide. The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 - 29 mL/min) is 0.25 mg taken orally once daily in combination with enzalutamide. No dose adjustment is required for patients with mild renal impairment.
Please see full U.S. Prescribing Information and Patient Information for TALZENNA® (talazoparib) at www.TALZENNA.com.
About XTANDI® (enzalutamide) and Important Safety Information
Please see the XTANDI Full Prescribing Information for additional safety information.
1 Key statistics for prostate cancer. American Cancer Society. https://www.cancer.org/cancer/prostate- cancer/about/key-statistics.html. Last updated January 12, 2022. Accessed October 26, 2023.
2 What are the symptoms of prostate cancer? Centers for Disease Control and Prevention. https://www.cdc.gov/cancer/prostate/basic_info/symptoms.htm. Last updated August 23, 2021. Accessed October 26, 2023.
3 Prostate Cancer: Types of Treatment. Cancer.net. https://www.cancer.net/cancer-types/prostate- cancer/types-treatment#advanced. Last updated December 2022. Accessed October 26, 2023.
4 Kirby M, et al. Int J Clin Pract. 2011;11:1180-1192.
5 Referenced with permission from the NCCN® Clinical Practice Guidelines in Oncology (NCCN®) for Prostate Cancer V.4.2023. © National Comprehensive Cancer Network®, Inc. 2023. All rights reserved. Accessed [December 27, 2023]. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
6 Herberts, C., Wyatt, A. W., Nguyen, P. L., & Cheng, H. H. (2023). Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair. American Society of Clinical Oncology Educational Book, 43(43), e390384–e390384. https://doi.org/10.1200/EDBK_390384.
7 de Bono JS, Mehra N, Scagliotti GV, Castro E, Dorff T, Stirling A, Stenzl A, Fleming MT, Higano CS, Saad F, Buttigliero C, van Oort IM, Laird AD, Mata M, Chen HC, Healy CG, Czibere A, Fizazi K. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol. 2021 Sep;22(9):1250-1264. doi: 10.1016/S1470-2045(21)00376-4. Epub 2021 Aug 10. Erratum in: Lancet Oncol. 2022 May;23(5):e207. Erratum in: Lancet Oncol. 2022 Jun;23(6):e249. PMID: 34388386.
8 Chung JH, Dewal N, Sokol E. Prospective comprehensive genomic profiling of primary and metastatic prostate tumors. JCO Precis Oncol 2019;3:PO.18.00283.
9 Scott, R. J., Mehta, A., Macedo, G. S., Borisov, P. S., Kanesvaran, R., & El Metnawy, W. (2021). Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget, 12(16), 1600–1614. https://doi.org/10.18632/oncotarget.28015.
10 2023 TALZENNA [package insert]. New York, NY: Pfizer Inc.
*NCCN=National Comprehensive Cancer Network® (NCCN®)