ESMO: Lynparza Provides 31% Survival Improvement in Prostate Cancer Indications
Lynparza reduced the risk of death in patients with a certain kind of prostate cancer by 31%, AstraZeneca and Merck announced. The overall survival benefit of the drug was shared this weekend, four months after the U.S. Food and Drug Administration approved it as a treatment for prostate cancer.
On Sunday, the two companies presented data from the Phase III PROfound trial that earned the approval for Lynparza in this indication at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. Data shared during the conference, and also published in The New England Journal of Medicine, showed that Lynparza demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus Xtandi (enzalutamide) or Zytiga (abiraterone) in men with metastatic castration-resistant prostate cancer (mCRPC) who have BRCA1/2 or ATM gene mutations. Patients in the Phase III study had previously been treated with enzalutamide and/or abiraterone.
Lynparza reduced the risk of death in men with BRCA1/2 or ATM gene mutations by 31% in comparison to retreatment with the other two drugs. Overall survival was a key secondary endpoint of the Phase III study. Median OS was 19.2 months for patients treated with Lynparza and 14.7 months for enzalutamide or abiraterone. Merck and AstraZeneca noted that 66% of the men in the Phase III study crossed over to receive treatment with Lynparza after their disease progressed on the other two medications.
An exploratory analysis also showed a non-statistically significant improvement in OS in the overall trial population of men with HRR gene mutations, which includes BRCA1/2, ATM, CDK12 and 11 other HRR-mutated genes. In those patients, the risk of death was reduced by 31% for Lynparza patients compared to the other control drugs. Median overall survival for these patients was 17.3 months compared to 14 months for enzalutamide or abiraterone.
PARP inhibitors are designed to disable DNA repair pathways in cancer cells, which make it difficult for those cells to survive. Lynparza is a first-in-class PARP inhibitor. It is the first targeted treatment that blocks DNA damage response in cells and tumors that have a deficiency in homologous recombination repair (HRR), such as BRCA1 and BRCA2 mutations.
Prostate cancer is the second most common type of cancer in men, with an estimated 1.3 million new patients diagnosed across the globe in 2018. Approximately 20 to 30% of men with mCRPC have an homologous recombination repair (HRR) gene mutation, of which BRCA1/2 and ATM mutations are a subpopulation. Approximately 10 to 20% of early stage hormone-sensitive prostate cancer cases will develop into CRPC within approximately five years.
“The PROfound trial is the first positive Phase III trial using molecular biomarker testing to help identify treatment options for certain men with metastatic castration resistant prostate cancer. These results further underpin the importance of genomic testing for HRR gene mutations to help identify this at-risk patient population and help physicians make treatment decisions. These results demonstrate the potential of Lynparza for mCRPC patients with certain HRR mutations,” Roy Baynes, head of global clinical development, chief medical officer at Merck Research Laboratories said in a statement.
José Baselga, head of Oncology R&D at AstraZeneca, added that the trial results will help transform the treatment landscape for men with metastatic castration-resistant prostate cancer. He said Lynparza is the only PARP inhibitor to demonstrate overall survival versus enzalutamide or abiraterone for men with BRCA or ATM mutations and the companies look forward to providing this treatment opportunity to patients.
AstraZeneca and Merck are exploring additional trials in metastatic prostate cancer including the ongoing Phase III PROpel trial, with first data expected in 2021, evaluating Lynparza as a first-line medicine for patients with mCRPC in combination with abiraterone acetate versus abiraterone acetate alone.
Days before Lynparza was approved for this indication, Clovis Oncology’s Rubraca was greenlit for patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.