The approval is based on results from a Phase III study of PROpel showing that combination with Lynparza
77% lower risk of disease progression or death compared with abiraterone alone
Japan's first PARP inhibitor approved for clinical demonstration
Significant advantages in combination with novel hormone preparations
AstraZeneca and MerckLympaz(olaparib) in combination with abiraterone and prednisolone is approved in Japan for the treatment of adult patients with BRCA-mutated (BRCAm) castration-resistant prostate cancer with distant metastases (mCRPC).
Approval by the Japanese Ministry of Health, Labor and Welfare was based on a subgroup analysisPROpel-Phase III studywhat does this showLympazThe combination with abiraterone demonstrated highly clinically significant improvements in radiographic progression-free survival (rPFS) and overall survival (OS) in patients with BRCA mutations compared to abiraterone alone.
Prostate cancer is the most common cancer among men in Japan and the sixth leading cause of cancer death in the region.1Despite multiple treatment options, the prognosis of mCRPC remains poor, and options are limited for patients whose cancer progresses after initial therapy.1,2
"The PROpel study showed that the combinationLympazThe combination of abiraterone produced a clinically meaningful improvement in outcomes in patients with BRCA-mutated metastatic castration-resistant prostate cancer. With this approval, Japanese patients now have the opportunity to benefit from this new treatment combination, which has the potential to become a new standard of care for patients with BRCA mutations. "
Dave Fredrickson, EVP Oncology, AstraZeneca, sagte: "DeathLympazThe combination has been shown to reduce the risk of disease progression or death compared with standard of care and underscores the critical importance of BRCA testing in diagnosing metastases. Today's approval is a major advance for Japanese patients with BRCA-mutated metastatic castration-resistant prostate cancer who urgently need new first-line treatment options. "
“Prostate cancer affects thousands of patients in Japan each year, and currently patients with metastatic disease have limited options,” said Eliav Barr, senior vice president, global clinical development head, and chief medical officer, Merck Research Laboratories. Metastatic castration for BRCA mutations It is important to develop and deliver new treatment combinations to improve the current standard of care for patients with resistant prostate cancer. "
When analyzing the subgroups of PROpel, the results show thatLympazAdding abiraterone reduced the risk of disease progression or death by 77% (based on hazard ratio [HR] 0.23; 95% confidence interval [CI] 0.12-0.43) and reduced the risk of death by 61% (based on HR) compared to compared with abiraterone in BRCam-mCRPC patients (0.39, 95% CI 0.16-0.86). Patients treated with this drug did not achieve mean rPFS and mean OSLympazThe median duration was 8.4 months for patients treated with abiraterone plus and 23.6 months for patients treated with abiraterone alone.
Safety and TolerabilityLympazAbiraterone in PROpel was consistent with previous clinical trial results and the known profile of each drug.
LympazBased on the PROpel study, it is approved in the European Union (EU) and several other countries in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC who are not clinically suitable for chemotherapy. The combination is also approved in the U.S. for the treatment of adult patients with malignant or suspected malignant BRCAm-mCRPC.
LympazMonotherapy for BRCam-mCRPC patients has also been approved in Japan based on results fromPROfound Phase III Study. It is approved in the EU and China for the same indication as in the US for the treatment of mCRPC with homologous recombination (HRR) mutations (BRCA and other HRR gene mutations) after treatment with enzalutamide or abiraterone patients with progressive disease.
Prostate cancer is the second most common cancer in men and the fifth leading cause of cancer death in men worldwide, with an incidence of 1.4 million and 375,000 deaths in 2020.3,4In 2022, Japan has an estimated 96,400 new cases and 13,300 deaths.2,5Overall survival for patients with mCRPC was about three years in clinical trials and even shorter in practice.6About half of mCRPC patients may receive only one effective treatment, and those who proceed to further treatment often benefit less from subsequent treatments.7-12 (display, other).
castration-resistant metastatic prostate cancer
Metastatic prostate cancer is associated with significant mortality.13The development of prostate cancer is often triggered by male sex hormones, so-called androgens, including testosterone.14
In men with mCRPC, prostate cancer can grow and spread to other parts of the body despite the use of androgen deprivation therapy to block the effects of male sex hormones.15Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these will have metastasized at the time of CRPC diagnosis.16Among patients without metastases at the time of CRPC diagnosis, 33% were likely to develop metastases within two years.16
Despite advances in the past decade in the treatment of mCRPC with taxane therapy and novel endocrine disruptors (NHAs), there are still significant unmet needs in this population.15-18 (view, professional).
PROpel is a Phase III, randomized, double-blind, multicenter study evaluating efficacy, safety and tolerabilityLympazIn men with mCRPC not receiving chemotherapy or NHA, when combined with abiraterone and prednisone or prednisolone compared with placebo.
The primary endpoint was rPFS, and secondary endpoints included OS, time to secondary progression or death, and time to first subsequent treatment. In September 2021, at a planned interim analysis, the independent data monitoring committee concluded that the PROpel study met its primary endpoint of rPFS.
More information about trial accessClinical Trial Network。
Lympaz(Olaparib) is a first-in-class PARP inhibitor and the first targeted therapy to block the DNA damage response (DDR) in HRR-deficient cells/tumors, such as those with BRCA1 and/or BRCA2 mutations. Caused by other substances such as NHA.
Inhibit PARPLympazLeads to capture of PARP bound to DNA single-strand breaks, stalling of replication forks, collapse of replication forks and formation of double-strand DNA breaks, and death of cancer cells.
LympazIt is currently approved in several countries for the maintenance treatment of multiple tumor types, including recurrent platinum-sensitive ovarian cancer, either as monotherapy or in combination with bevacizumab for BRCA-mutant (BRCam) and the same First-line maintenance therapy for source recombination repair deficiency. Human Resource Development). )-positive advanced ovarian cancer; germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan, this also includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this Including all BRCAm-HER2-negative high-risk early breast cancers); for gBRCam metastatic pancreatic cancer; in combination with abiraterone for metastatic castration-resistant prostate cancer (mCRPC) (EU) and BRCAm-mCRPC ( US); and as monotherapy for mCRPC with mutated HRR genes in patients whose disease has progressed on prior NHA therapy (BRCam in EU and Japan only). in China,LympazIt is approved for the treatment of BRCam-mCRPC and as first-line maintenance bevacizumab in HRD-positive advanced ovarian cancer.
LympazThe drug, jointly developed and marketed by AstraZeneca and Merck, has been used to treat more than 75,000 patients worldwide.LympazWith an extensive clinical trial development programme, AstraZeneca and Merck are collaborating to understand how it affects a variety of PARP-dependent tumors both as a monotherapy and as a combination therapy across multiple cancer types.LympazIs the basis of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.
Strategic oncology collaboration between AstraZeneca and Merck
In July 2017, AstraZeneca and Merck & Co., Kenilworth, NJ, USA (excluding the US and Canada) announced a Merck global strategic partnership to co-develop and co-commercializeLympaz, the world's first PARP inhibitor, andall is well(selumetinib) is a mitogen-activated protein kinase inhibitor used in the treatment of several types of cancer.
By working together, the company will growLympazIall is welland other potential new drugs as monotherapy and combination therapy. the company will developLympazIall is wellCombination independently with respective PD-L1 drug and PD-1.
AstraZeneca in Oncology
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