One would think the black box warnings will be extreme but the FDA has still approved Lynparza for metastatic, castration-resistant patients with Prostate cancer because of it's better efficacy then other present treatments.
Currently it is used for ovarian and breast cancers with annual sales of more than USD $1B.
It is hard to analyse because of the obvious frailty of the cohort but it is potentially leathal in 4% with another 36% of patients having serious adverse reactions.
I wonder if DEP® irinotecan in combination with Lynparza® (Olaparib) would achieve similar results as the lab trial Colon cancer outcomes did late last year and potentialy having less severe side effects?
Something for SPL to consider no doubt!
May 21, 2020 - AstraZeneca and Merck Receive Lynparza Boost
AstraZeneca (AZN) and Merck & Co. (MRK) announced that their Lynparza has received the FDA nod for its fourth tumor type, prostate cancer. This PARP inhibitor is now authorized to be used for treating patients with previously treated metastatic, castration-resistant patients with mutations in their homologous recombination repair (HRR) genes. Earlier, the companies had stated that the drug also topped Zytiga and Xtandi at extending the lives of patients suffering from BRCA1, BRCA2 or ATM mutations.
The application was supported by the data collected from the Phase 3 Profound study, which demonstrated that Lynparza was effective in reducing the risk of diseases progression or death by 51 percent in comparison to therapies such as Xtandi and Zytiga. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said, “LYNPARZA is the only PARP inhibitor approved with Phase III data for men with HRR gene-mutated metastatic castration-resistant prostate cancer. This approval highlights the importance of genomic testing to identify treatment options for men in this patient population.” The approval provides validation to the use of genomic testing for diagnosing prostate cancer.
The primary endpoint of the trial was radiographic progression-free survival (rPFS) in men with BRCA1/2 or ATM gene mutations. The data demonstrated that the drug lessened the risk of disease progression or death by 66%. It also improved rPFS to a median of 7.4 months versus 3.6 months with enzalutamide or abiraterone. One of the key secondary endpoints of the rPFS benefit in the overall HRR gene mutated trial population was also achieved by the drug. It also reduced the risk of disease progression or death by 51%.
4 percent of the patients treated with the drug showed fatal adverse reactions such as pneumonia, cardiopulmonary failure, aspiration pneumonia and intestinal diverticulum among others. 36 percent of the patients showed serious adverse reactions such as anemia, pulmonary embolism and fatigue. Patients administered with LYNPARZA and ADT had a 6% incidence of pulmonary embolism in comparison to 0.8% of patients given ADT plus either enzalutamide or abiraterone.
AstraZeneca and Merck are testing the drug in additional trials in prostate cancer. The ongoing Phase III PROpel trial is testing the drug as a 1st-line treatment in combination with abiraterone acetate for patients with mCRPC in comparison to using abiraterone acetate alone. PROfound is a prospective, multi-center, randomized, open-label, Phase III trial. The trial is designed to test the efficacy and safety of LYNPARZA 300 mg consisting of two 150 mg tablets, taken twice daily versus enzalutamide or abiraterone in patients with mCRPC. The trial aimed to analyze patients with HRRm genes in two groups.
AstraZeneca and Merck are collaborating to develop Lynparza for different indications. It has one of the most sophisticated and advanced clinical trial programs for any PARP inhibitor. The drug candidate is the targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair. The drug works by inhibiting PARP, leading to the trapping of PARP attached to DNA single-strand breaks. Lynparza is being tested for its potential to treat a wide range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.
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