Lynparza Reduces Death Risk by 31% in BRCA1/2 or ATM-Mutated mCRPC, Demonstrating Significant Overall Survival Benefit in PROfound Phase III Trial

September 21, 2020 /Bio ValleyBIOON/ ---AstraZeneca(AstraZeneca) recently at the 2020 European MedicalTumorThe final results of the Phase III PROfound study of the targeted anticancer drug Lynparza (Chinese brand name: Lipuzhuo; generic name: olaparib, olaparib tablets) were presented at the virtual European Society for Medical Oncology (ESMO) Congress. The data showed that in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 or ATM gene mutations who experienced disease progression after treatment with novel hormonal agents (NHAs)—a subgroup of patients with homologous recombination repair (HRR) gene mutations—Lynparza demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) compared to standard-of-care drugs Xtandi (enzalutamide) or Zytiga (abiraterone acetate).

Notably, Lynparza is the only PARP inhibitor that has demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC). Prostate cancer is the most common type of cancer in men, with an estimated 1.3 million new cases globally in 2018. Approximately 20–30% of male patients with mCRPC harbor HRR gene mutations.

For the key secondary endpoint of OS, Lynparza reduced the risk of death by 31% compared with Xtandi or Zytiga (HR=0.69; 95% CI: 0.50–0.97; p=0.0175). Although 66% of men in the NHA treatment group switched to Lynparza upon disease progression, the median OS was 19.1 months in the Lynparza arm versus 14.7 months in the Xtandi or Zytiga arm.

An exploratory analysis also showed that in the male study population with HRR gene mutations (BRCA1/2, ATM, CDK12, and 11 other HRR genes), Lynparza reduced the risk of death by 21% compared with Xtandi or Zytiga (HR=0.79; 95% CI: 0.61–1.03), although the improvement in OS was not statistically significant. The median OS was 17.3 months in patients treated with Lynparza versus 14.0 months in those treated with Xtandi or Zytiga.

Prostate Cancer (Image source: hopkinsmedicine.org)

Johann de Bono, one of the principal investigators of the PROfound study and Head of Drug Development at The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, stated: “In the PROfound study, Lynparza demonstrated significant clinical benefit across all key endpoints, with the final overall survival (OS) results reinforcing the drug’s potential to change the standard of care for men with mCRPC. This trial indicates that Lynparza will play a pivotal role in the new era of precision medicine in prostate cancer, providing molecularly targeted therapy for patients who previously had poor prognoses and limited treatment options.”

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated, “These results help change the treatment outlook for certain patients with metastatic castration-resistant prostate cancer (mCRPC), among whom it has been consistently difficult to achieve prolonged overall survival. Lynparza is the only PARP inhibitor proven to improve overall survival (OS) in patients with BRCA or ATM mutations compared to Xtandi and Zytiga. We look forward to continuing to bring Lynparza to these patients worldwide.”

In August 2019, the PROfound study met its primary endpoint, with data showing that Lynparza significantly improved radiological progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 or ATM gene mutations, thereby achieving the key secondary endpoint of improving rPFS across the entire population of patients with homologous recombination repair gene mutations (HRRm). Based on these data, Lynparza was approved in the United States in May 2020FDAApproval of New Indication: For patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after treatment with novel hormonal therapy (NHT) Xtandi or Zytiga and carry deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) mutations. It is estimated that approximately 20-30% of mCRPC patients carry HRR gene mutations.

Lynparza was first approved in December 2014 as the world’s first PARP inhibitor to reach the market, and this latest approval opens up a new therapeutic area for the drug. Lynparza is now indicated for the treatment of four types of cancer, including ovarian cancer,Breast Cancer, pancreatic cancer, prostate cancer.LynparzaLynparza can selectively kill cancer cells by exploiting defects in the tumor DNA damage repair (DDR) pathway, a mechanism of action that endows Lynparza with the potential to treat a broad spectrum of tumors harboring DNA damage repair deficiencies.

In July 2017, AstraZeneca and Merck & Co. entered into a global strategic collaboration in oncology to jointly develop and commercialize Lynparza and another MEK inhibitor, selumetinib, for the treatment of various types of cancer. Within the class of PARP inhibitors, Lynparza has the broadest and most advancedClinical TrialDevelopment Project. Currently, both parties are collaborating to investigate Lynparza as a monotherapy and in combination therapy for a broad range ofTumortherapeutic potential.

In the Chinese market, Lynparza (Lynparza) was approved in August 2018 for maintenance treatment of platinum-sensitive recurrent ovarian cancer. As the first targeted therapy approved for ovarian cancer in China, Lynparza marked the entry of PARP inhibitors into the era of ovarian cancer treatment in the country. In early December 2019, Lynparza received further approval for first-line maintenance treatment in patients with BRCA-mutated advanced ovarian cancer. Benefiting from China’s strong support for pharmaceutical innovation and accelerated approval of urgently needed new drugs, Lynparza became the first PARP inhibitor approved in China for first-line maintenance therapy in ovarian cancer. On November 28, 2019, Lynparza was included in the National Reimbursement Drug List. (Bioon.com)

Original Source: Lynparza Reduced the Risk of Death by 31% in BRCA1/2 or ATM-Mutated Metastatic Castration-Resistant Prostate Cancer in the PROfound Phase III Trial