Treatment of BRCA1/2 or ATM gene mutated metastatic castration resistant prostate cancer: Lynparza granted Breakthrough Therapy designation by FDA
The FDA ( Food and Drug Administration ) has granted Breakthrough Therapy designation ( BTD ) for the oral poly ADP-ribose polymerase ( PARP ) inhibitor Lynparza ( Olaparib ), for the monotherapy treatment of BRCA1/2 or ATM gene mutated metastatic castration resistant prostate cancer ( mCRPC ) in patients who have received a prior taxane-based chemotherapy and at least one newer hormonal agent ( Abiraterone or Enzalutamide ).
The FDA criteria for BTD require preliminary clinical evidence that demonstrates a drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
The decision to assign a Breakthrough Therapy designation for Lynparza is based on the results of the TOPARP-A phase II trial, which found that Olaparib monotherapy in metastatic castration resistant prostate cancer may offer substantial improvement over available therapies for the treatment of the biomarker-selected population with this serious and life-threatening condition.
The TOPARP-A trial showed that men with prostate cancer with defective DNA damage repair mechanisms responded to Olaparib.
Once prostate cancer has progressed to mCPRPC, treatment focuses on extending life, delaying disease progression, and improving symptoms and quality of life.
Overall survival time for patients treated with chemotherapy and newer hormonal agents is 10 months.
There are also no approved therapies for third line and above ( 3L+ ) mCRPC patients, and no targeted therapies are available for mCRPC patients with somatic or germline mutations in BRCA1, BRCA2 or ATM.
Olaparib is an innovative, first-in-class oral poly ADP-ribose polymerase ( PARP ) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells.
This mode of action gives Olaparib the potential for activity in a range of tumour types with DNA repair deficiencies.
Lynparza has been approved for the maintenance treatment of women with BRCA-mutated ovarian cancer. ( Xagena )
Source: AstraZeneca, 2016