PATIENTS IN SCOTLAND WITH AN ADVANCED FORM OF PROSTATE CANCER CAN NOW ACCESS LYNPARZA (OLAPARIB) WITH ABIRATERONE AND PREDNISONE OR PREDNISOLONE WITHOUT A BIOMARKER TEST
- Olaparib with abiraterone and prednisone or prednisolone becomes the first and only combination therapy to be accepted for use in Scotland for adult patients with metastatic castration resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated, regardless of biomarker status.[1]
- Acceptance by the Scottish Medicines Consortium (SMC) is based on pivotal data from the PROpel Phase III trial which illustrated olaparib as the first PARP inhibitor in combination with abiraterone and prednisone or prednisolone to reduce the risk of disease progression or death by more than a third (34%) in this setting.[2]
- Safety and tolerability was in line with prior clinical trials and the known profiles of the individual medicines.2
- Prostate cancer is the most common cancer among Scottish males, affecting 1 in 10 men.[3] Around 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years and at least 84% of these patients will have metastases at the time of CRPC diagnosis.[4]
London, UK, Monday 11 March 2024 – AstraZeneca and MSD (tradename of Merck & Co., Inc., Rahway, N.J., USA [NYSE: MRK]) today announced that the Scottish Medicines Consortium (SMC) has accepted Lynparza (olaparib) for use as combination therapy with abiraterone and prednisone or prednisolone for adult patients with metastatic castration resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated, regardless of biomarker status.1
Prostate cancer is the most common cancer among Scottish males, affecting 1 in 10 men.3 Approximately 10-20% of these can be classified as castration resistant (CRPC), evolving to resist the standard of care (SOC), androgen deprivation therapy (ADT).4 When CRPC is at an advanced or metastasised stage (mCRPC), meaning it has spread to other parts of the body, it is typically hard to treat, resulting in a poor prognosis.[5],[6]
Professor Robert Jones, Professor of Clinical Cancer Research, University of Glasgow, said:
“Currently there is no cure for advanced prostate cancer which often leads to poor prognosis. This acceptance by the SMC marks a milestone for men living with this specific type of prostate cancer as pivotal data from the PROpel Phase III trial have shown that olaparib combination therapy significantly reduced the risk of disease progression compared to placebo and abiraterone.”
Roughly half of patients with mCRPC only ever receive one line of therapy and there is an urgent unmet need for new treatments in the first-line treatment of mCRPC to optimise patient outcomes.[7] Olaparib works by inhibiting PARP proteins to disrupt the DNA-repair process and without these proteins, cancer cells may become too damaged to survive and die.[8]
This SMC acceptance is based on pivotal data from the PROpel Phase III clinical trial.2 In the planned primary analysis of the trial at first data cutoff, median imaging-based progression-free survival (ibPFS) was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs 16.6 months) and gave a 34% reduction in the risk of progression or death (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.54 to 0.81; p<0.001).2
Tom Keith-Roach, President, AstraZeneca UK, said: “Today’s decision by the SMC is hugely welcome. Extending access for olaparib, a product of British science already available to patients in England and Wales, to eligible patients in Scotland adds a much-needed new treatment option in an area with continued high unmet clinical need."
David Long, Head of Oncology at MSD UK, said: “Prostate cancer remains the most common cancer in men in Scotland and unfortunately patients with advanced disease can face an uncertain future. We are delighted that patients with advanced prostate cancer can now access olaparib without the need for a biomarker test, and we look forward to working with Scottish clinicians to offer this medicine to every eligible patient as fast as possible."
The safety and tolerability of Lynparza plus abiraterone and prednisone or prednisolone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. At the time of this updated analysis, there were no new long-term safety issues identified.2
The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy (≥ 10%) were nausea, fatigue/asthenia, anaemia, vomiting, diarrhoea, decreased appetite, headache, neutropenia, dysgeusia, cough, leukopenia, dizziness, dyspnoea, and dyspepsia.8 The Grade ≥3 adverse reactions occurring in > 2% of patients were anaemia (14%), neutropenia (5%), fatigue/asthenia (4%), leukopenia (2%) and thrombocytopenia (2%).8
[1] Scottish Medicine Consortium. Olaparib in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. Detailed advice document SMC2617 – published 11 March 2024
[2] Clarke NW, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence 2022;1(9).
[3] Prostate Cancer. Prostate Scotland. Available at: https://www.prostatescotland.org.uk/disease-tests-and-treatments/prostate-cancer. Last accessed: March 2024.
[4] Kirby M, et al. Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice. 2021;65(11):1180-1192.
[5] Advanced Prostate Cancer. Urology Care Foundation. Available at: https://www.urologyhealth.org/urology-a-z/a_/advanced-prostate-cancer. Last accessed: March 2024
[6] Posdzich P, et al. Metastatic Prostate Cancer—A Review of Current Treatment Options and Promising New Approaches. 2023 Jan;15(2):461.
[7] George D, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. 2020 Jan;18(4):284-294.
[8] Electronic Medicines Compendium (EMC). Lynparza 100 mg film-coated tablets – Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/9204/smpc#gref. Last accessed: March 2024.
About Lynparza
Olaparib is a potent inhibitor of human poly (ADP-ribose) polymerase (PARP) enzymes that is targeted to block DNA repair in cancer cells harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2.8 Inhibition of PARP proteins with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse, and the generation of DNA double-strand breaks (DSBs) and cancer cell death.8
Lynparza (olaparib) is indicated in the United Kingdom for the treatment of prostate cancer as:
- combination therapy with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.8
- monotherapy for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2-mutations (germline and/or somatic) who have progressed following prior therapy that included a new hormonal agent.8
For more information about olaparib, a summary of product characteristics (SmPC) can be found here: https://www.medicines.org.uk/emc/product/9204/smpc#gref.
About PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of olaparib versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the first line setting.[9]
Men in both treatment groups will also receive either prednisone or prednisolone twice daily.9 The primary endpoint is radiographic progression-free survival (rPFS), and secondary endpoints include overall survival (OS), time to disease progression or death (PFS2), and time to first subsequent therapy (TFST).9
Over 700 patients globally were randomised in PROpel in a 1:1 ratio to treatment with either olaparib and abiraterone or placebo and abiraterone.9
Patients receive oral treatment with olaparib 300 mg twice daily + abiraterone 1000 mg once daily or placebo twice daily + abiraterone 1000 mg once daily.9 Patients in both treatment groups also receive either prednisone 5 mg twice daily or prednisolone 5 mg twice daily.9
For more information about the trial please visit ClinicalTrials.gov.
About Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.[10] Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.[11]
In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.4 Approximately 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these patients will have metastases at the time of CRPC diagnosis.4
Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.4 Despite the advances in mCRPC treatments in the past decade with taxanes and new hormonal agents (NHAs), median progression free survival in clinical trial settings for these patients is up to 20 months, though may be shorter in the real-world setting, with approximately 50% of patients only receiving one life-prolonging therapy.2,[12],[13],[14] Hence there is a high unmet medical need for new first line treatments in this patient population.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.
With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS.
For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.
About MSD
At MSD, known as Merck & Co., Inc., Rahway, NJ, USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information, visit www.msd-uk.com and connect with us @MSDintheUK on Twitter, LinkedIn, Instagram, YouTube and Facebook.
[9] ClinicalTrials.gov. Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer. Available at: https://clinicaltrials.gov/ct2/show/NCT03732820. Last accessed: March 2024.
[10] Chowdhury S, et al. Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer: the prostate cancer registry. Target Oncol. 2020;15(3):301-15.
[11] Cancer.Net. Treatment of metastatic castration-resistant prostate cancer. Available at: www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer. Last accessed: March 2024.
[12] Rathkopf DE, et al. Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302). Europe Urology. 2014;66(5):815-825
[13] Beer TM, et al. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study. European Urology. 2017;71(2):151-154
[14] Tannock IF, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004; 351:1502-1512
