AstraZeneca, Merck presents results from Phase 3 PROfound trial of LYNPARZA
AstraZeneca (AZN) and Merck (MRK) presented detailed results from the Phase 3 PROfound trial in 387 men with metastatic castration-resistant prostate cancer who have a mutation in their homologous recombination repair genes and whose disease had progressed on prior treatment with new hormonal agent treatments e.g. abiraterone or enzalutamide.
The trial was designed to analyze men with mCRPC harboring HRR-mutated genes in two cohorts: the primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if LYNPARZA showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes.
Results showed a statistically-significant and clinically-meaningful improvement with LYNPARZA in the primary endpoint of radiographic progression-free survival in BRCA1/2 or ATM-mutated tumors reducing the risk of disease progression or death by a median of 7.4 months versus 3.6 months for those receiving abiraterone or enzalutamide.
LYNPARZA reduced the risk of disease progression or death by 66% for these men. The trial also met the key secondary endpoint of rPFS in the overall HRRm population, where LYNPARZA reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months for those receiving abiraterone or enzalutamide.
In the key secondary endpoint of time to pain progression, median TTPP was not reached with LYNPARZA and was 9.92 months with abiraterone and enzalutamide in patients with BRCA1/2 or ATM mutations.
Results also showed a trend at this interim analysis time point for improvement in overall survival, another key secondary endpoint. LYNPARZA extended OS to a median of 18.5 months versus 15.1 months for abiraterone or enzalutamide in men with BRCA1/2 or ATM-mutated tumors, of which 81% started on abiraterone or enzalutamide and, following confirmed disease progression, then switched to LYNPARZA.
At this interim analysis, the OS endpoint did not meet statistical significance. In an exploratory analysis, a similar trend in OS was observed at this interim analysis in the HRRm population with a median of 17.5 months for men treated with LYNPARZA vs. 14.3 months for those receiving abiraterone or enzalutamide.
The trial showed a confirmed overall response rate a key secondary endpoint of 33.3% for LYNPARZA vs. 2.3% for abiraterone or enzalutamide in patients with BRCA1/2 or ATM mutations.
In an exploratory analysis of patients in the overall HRRm population, confirmed ORR was 21.7 % for LYNPARZA vs. 4.5% for patients receiving abiraterone or enzalutamide. The safety and tolerability profile of LYNPARZA in the PROfound trial was in line with that observed in prior clinical trials.
The most common adverse events greater than or equal to20% for LYNPARZA compared to abiraterone or enzalutamide were anemia, nausea, fatigue and asthenia, decreased appetite, and diarrhea. Grade 3 or above AEs were anemia, fatigue and asthenia, vomiting, dyspnea, urinary tract infection, nausea, decreased appetite, diarrhea, and back pain. AEs led to discontinuation of treatment in 16% of patients on LYNPARZA vs. 9% on abiraterone and enzalutamide.
AstraZeneca and Merck are also exploring additional trials in prostate cancer, including the ongoing Phase 3 PROpel trial, evaluating LYNPARZA as a first-line therapy in mCRPC for patients with or without HRR mutations, in combination with abiraterone acetate.
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