- TALZENNA + XTANDI is the first PARP inhibitor plus ARPI combination to demonstrate statistically significant and clinically meaningful improvement in overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of HRR mutation status
- TALZENNA + XTANDI improved median OS by almost 9 months in unselected patients (Cohort 1) and by 14 months in patients selected for HRR mutations (Cohort 2) versus standard of care XTANDI
NEW YORK, NY, USA I February 13, 2025 I Pfizer Inc. (NYSE: PFE) today announced positive results from the Phase 3 TALAPRO-2 study of TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) compared to placebo plus XTANDI in patients with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations. The TALAPRO-2 results will be presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco and featured in the ASCO GU official Press Program.
The TALAPRO-2 study evaluated two sets of patients, unselected (cohort 1) and selected for HRR gene-mutations (cohort 2). Overall survival was a prespecified, alpha-protected key secondary endpoint. After more than four years of median follow-up (52.5 months), the median OS in cohort 1 was 45.8 months with TALZENNA in combination with XTANDI, and 37.0 months with XTANDI and placebo (Hazard Ratio [HR] of 0.80; 95% Confidence Interval [CI], 0.66-0.96; p=0.015), representing a 20% reduction in the risk of death. This represents a nearly 9-month gain in median OS versus standard of care XTANDI. Data from cohort 1 will be presented today at ASCO GU in an oral presentation (Abstract LBA18) by Dr. Neeraj Agarwal, global lead investigator for TALAPRO-2.
In Cohort 2, a statistically significant and clinically meaningful improvement in OS was observed in patients with HRR-mutated mCRPC. At a median follow-up of 44.2 months, the median OS was 45.1 months with TALZENNA in combination with XTANDI, and 31.1 months with XTANDI and placebo (HR of 0.62; 95% CI, 0.48-0.81; p=0.0005), a 38% reduction in the risk of death. This result represents a 14-month gain in median OS versus standard of care XTANDI in a patient population with a historically poor prognosis. The OS improvement in the HRR-mutated population was observed in patients in both BRCA and non-BRCA gene alterations. Dr. Karim Fizazi, Institut Gustave Roussy, University of Paris-Saclay will share data from Cohort 2 at ASCO GU today (Abstract LBA141).
“Since its approval, TALZENNA in combination with XTANDI has redefined the standard of care for those living with homologous recombination repair gene-mutated mCRPC. These latest data from TALAPRO-2 are extremely compelling, demonstrating that the combination significantly extended overall survival, in patients selected and unselected for HRR gene alterations, potentially shifting the treatment paradigm for all men living with mCRPC,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “Although definitive conclusions cannot be drawn across studies, these results appear to represent the longest median overall survival reported in a randomized, controlled Phase 3 trial in mCRPC. We look forward to continuing to work with global authorities to potentially update the TALZENNA label with these results.”
“TALAPRO-2 is the first study demonstrating a significant and clinically meaningful survival benefit using a combination of PARP and androgen receptor inhibitors in mCRPC,” said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2. “Survival rates in metastatic castration-resistant prostate cancer are poor due to the advanced and aggressive stage of the disease. Today’s results demonstrate the potential for TALZENNA in combination with XTANDI to be a practice-changing treatment to help improve patient survival in mCRPC.”
At the time of the final analysis, updated radiographic progression free survival (rPFS) and other secondary efficacy endpoints demonstrated maintained clinical benefit in both cohorts and were consistent with the primary analyses previously reported and published in The Lancet and Nature Medicine.
In addition to the FDA, these data have been shared with the European Medicines Agency (EMA) and other global health authorities to support potential updates of the approved labels for TALZENNA.
The safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. The most common all-cause adverse events in the TALZENNA group (≥30% of patients) were anemia, neutropenia, and fatigue, and the most common (≥10% of patients) grade 3–4 adverse events were anemia (49%) and neutropenia (19.3%). Adverse events were generally manageable with dose modification and supportive care.
About Metastatic Castration-Resistant Prostate Cancer
Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death among men worldwide, with an estimated 1.4 million new cases diagnosed in 2022.1 In the U.S., it is the most common cancer in men.2 mCRPC is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Approximately 10–20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis.3 Between 1.2–2.1% of all prostate cancer cases globally are mCRPC.4
About TALAPRO-2
The Phase 3 TALAPRO-2 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,035 unique patients with mCRPC who had not received new life-prolonging systemic treatments after documentation of mCRPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: unselected (n=805, of whom 169 had HRR mutations and 636 did not) and those with HRR gene mutations (n=399, including 169 patients from Cohort 1 and 230 subsequently enrolled to comprise Cohort 2). Patients with castrate testosterone levels were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day.
The primary endpoint of the trial was rPFS, defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent central review (BICR), or death, whichever occurred first, in both Cohort 1 (unselected) and Cohort 2 (those with HRRm). Secondary endpoints included OS, objective response rate (ORR), duration of response (DoR), prostate-specific antigen (PSA) response, time to cytotoxic chemotherapy and PFS2.
For more information on the TALAPRO-2 trial (NCT03395197), go to www.clinicaltrials.gov.
About TALZENNA® (talazoparib)
TALZENNA is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.
TALZENNA was initially approved in the U.S., EU, and multiple other regions as a single agent for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer.
TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA is the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations. TALZENNA in combination with XTANDI is now approved in more than 40 countries globally for patients with mCRPC, indications vary by country.
TALZENNA® (talazoparib) Indication in the U.S.
TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:
HRR gene-mutated mCRPC:
- In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Breast Cancer:
- As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.
Please see full U.S. Prescribing Information and Patient Information for TALZENNA ® (talazoparib) at www.TALZENNA.com.
About XTANDI ® (enzalutamide) and Important Safety Information
XTANDI® (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic castration-sensitive prostate cancer (mCSPC; also known as metastatic hormone-sensitive prostate cancer or mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the U.S., EU, and Japan. Over one million patients have been treated with XTANDI globally.6
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI ® (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
References
- Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians . 2024;74(3):229-263. Published 2024 April 4. doi: 10.3322/caac.21834
- American Cancer Society. Key Statistics for Prostate Cancer. Accessed August 2024. *other than non-melanoma skin cancer
- Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011 Nov;65(11):1180-92. doi: 10.1111/j.1742-1241.2011.02799.x. PMID: 21995694.
- Shore N, Oliver L, Shui I, Gayle A, Wong OY, Kim J, Payne S, Amin S, Ghate S. Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations. J Urol. 2021 Apr;205(4):977-986. doi: 10.1097/JU.0000000000001570. Epub 2020 Dec 17. PMID: 33332152. https://www.auajournals.org/doi/10.1097/JU.0000000000001570
- National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Prostate Cancer, Bethesda, MD, USA (2022); USA. Accessed December 2024. https://seer.cancer.gov/statfacts/html/prost.html.
- Data on file. Northbrook, IL: Astellas Inc.
SOURCE: Pfizer
Post Views: 118
- TALZENNA + XTANDI is the first PARP inhibitor plus ARPI combination to demonstrate statistically significant and clinically meaningful improvement in overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of HRR mutation status
- TALZENNA + XTANDI improved median OS by almost 9 months in unselected patients (Cohort 1) and by 14 months in patients selected for HRR mutations (Cohort 2) versus standard of care XTANDI
NEW YORK, NY, USA I February 13, 2025 I Pfizer Inc. (NYSE: PFE) today announced positive results from the Phase 3 TALAPRO-2 study of TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) compared to placebo plus XTANDI in patients with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations. The TALAPRO-2 results will be presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco and featured in the ASCO GU official Press Program.
The TALAPRO-2 study evaluated two sets of patients, unselected (cohort 1) and selected for HRR gene-mutations (cohort 2). Overall survival was a prespecified, alpha-protected key secondary endpoint. After more than four years of median follow-up (52.5 months), the median OS in cohort 1 was 45.8 months with TALZENNA in combination with XTANDI, and 37.0 months with XTANDI and placebo (Hazard Ratio [HR] of 0.80; 95% Confidence Interval [CI], 0.66-0.96; p=0.015), representing a 20% reduction in the risk of death. This represents a nearly 9-month gain in median OS versus standard of care XTANDI. Data from cohort 1 will be presented today at ASCO GU in an oral presentation (Abstract LBA18) by Dr. Neeraj Agarwal, global lead investigator for TALAPRO-2.
In Cohort 2, a statistically significant and clinically meaningful improvement in OS was observed in patients with HRR-mutated mCRPC. At a median follow-up of 44.2 months, the median OS was 45.1 months with TALZENNA in combination with XTANDI, and 31.1 months with XTANDI and placebo (HR of 0.62; 95% CI, 0.48-0.81; p=0.0005), a 38% reduction in the risk of death. This result represents a 14-month gain in median OS versus standard of care XTANDI in a patient population with a historically poor prognosis. The OS improvement in the HRR-mutated population was observed in patients in both BRCA and non-BRCA gene alterations. Dr. Karim Fizazi, Institut Gustave Roussy, University of Paris-Saclay will share data from Cohort 2 at ASCO GU today (Abstract LBA141).
“Since its approval, TALZENNA in combination with XTANDI has redefined the standard of care for those living with homologous recombination repair gene-mutated mCRPC. These latest data from TALAPRO-2 are extremely compelling, demonstrating that the combination significantly extended overall survival, in patients selected and unselected for HRR gene alterations, potentially shifting the treatment paradigm for all men living with mCRPC,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “Although definitive conclusions cannot be drawn across studies, these results appear to represent the longest median overall survival reported in a randomized, controlled Phase 3 trial in mCRPC. We look forward to continuing to work with global authorities to potentially update the TALZENNA label with these results.”
“TALAPRO-2 is the first study demonstrating a significant and clinically meaningful survival benefit using a combination of PARP and androgen receptor inhibitors in mCRPC,” said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2. “Survival rates in metastatic castration-resistant prostate cancer are poor due to the advanced and aggressive stage of the disease. Today’s results demonstrate the potential for TALZENNA in combination with XTANDI to be a practice-changing treatment to help improve patient survival in mCRPC.”
At the time of the final analysis, updated radiographic progression free survival (rPFS) and other secondary efficacy endpoints demonstrated maintained clinical benefit in both cohorts and were consistent with the primary analyses previously reported and published in The Lancet and Nature Medicine.
In addition to the FDA, these data have been shared with the European Medicines Agency (EMA) and other global health authorities to support potential updates of the approved labels for TALZENNA.
The safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. The most common all-cause adverse events in the TALZENNA group (≥30% of patients) were anemia, neutropenia, and fatigue, and the most common (≥10% of patients) grade 3–4 adverse events were anemia (49%) and neutropenia (19.3%). Adverse events were generally manageable with dose modification and supportive care.
About Metastatic Castration-Resistant Prostate Cancer
Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death among men worldwide, with an estimated 1.4 million new cases diagnosed in 2022.1 In the U.S., it is the most common cancer in men.2 mCRPC is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Approximately 10–20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis.3 Between 1.2–2.1% of all prostate cancer cases globally are mCRPC.4
About TALAPRO-2
The Phase 3 TALAPRO-2 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,035 unique patients with mCRPC who had not received new life-prolonging systemic treatments after documentation of mCRPC at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: unselected (n=805, of whom 169 had HRR mutations and 636 did not) and those with HRR gene mutations (n=399, including 169 patients from Cohort 1 and 230 subsequently enrolled to comprise Cohort 2). Patients with castrate testosterone levels were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day.
The primary endpoint of the trial was rPFS, defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent central review (BICR), or death, whichever occurred first, in both Cohort 1 (unselected) and Cohort 2 (those with HRRm). Secondary endpoints included OS, objective response rate (ORR), duration of response (DoR), prostate-specific antigen (PSA) response, time to cytotoxic chemotherapy and PFS2.
For more information on the TALAPRO-2 trial (NCT03395197), go to www.clinicaltrials.gov.
About TALZENNA® (talazoparib)
TALZENNA is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.
TALZENNA was initially approved in the U.S., EU, and multiple other regions as a single agent for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer.
TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA is the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations. TALZENNA in combination with XTANDI is now approved in more than 40 countries globally for patients with mCRPC, indications vary by country.
TALZENNA® (talazoparib) Indication in the U.S.
TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:
HRR gene-mutated mCRPC:
- In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Breast Cancer:
- As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.
Please see full U.S. Prescribing Information and Patient Information for TALZENNA ® (talazoparib) at www.TALZENNA.com.
About XTANDI ® (enzalutamide) and Important Safety Information
XTANDI® (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic castration-sensitive prostate cancer (mCSPC; also known as metastatic hormone-sensitive prostate cancer or mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the U.S., EU, and Japan. Over one million patients have been treated with XTANDI globally.6
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI ® (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
References
- Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians . 2024;74(3):229-263. Published 2024 April 4. doi: 10.3322/caac.21834
- American Cancer Society. Key Statistics for Prostate Cancer. Accessed August 2024. *other than non-melanoma skin cancer
- Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011 Nov;65(11):1180-92. doi: 10.1111/j.1742-1241.2011.02799.x. PMID: 21995694.
- Shore N, Oliver L, Shui I, Gayle A, Wong OY, Kim J, Payne S, Amin S, Ghate S. Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations. J Urol. 2021 Apr;205(4):977-986. doi: 10.1097/JU.0000000000001570. Epub 2020 Dec 17. PMID: 33332152. https://www.auajournals.org/doi/10.1097/JU.0000000000001570
- National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Prostate Cancer, Bethesda, MD, USA (2022); USA. Accessed December 2024. https://seer.cancer.gov/statfacts/html/prost.html.
- Data on file. Northbrook, IL: Astellas Inc.
SOURCE: Pfizer
Post Views: 118
