FDA News

FDA grants priority review to Lynparza for prostate cancer subtype

The FDA granted priority review to olaparib for the treatment of men with metastatic castration-resistant prostate cancer and homologous recombination repair gene mutations who progressed on treatment with a new hormonal agent, according to a press release from the agent’s manufacturers.

Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor.

The FDA based its decision, in part, on data from the randomized phase 3 PROfound study presented in September at European Society for Medical Oncology Congress.

The trial met its primary endpoint, based on significantly longer median radiographic PFS among men with BRCA1/BRCA2- or ATM-mutated metastatic castration-resistant prostate cancer assigned olaparib vs. physician’s choice of enzalutamide (Xtandi; Astellas, Pfizer) or abiraterone acetate (Zytiga, Janssen; 7.4 months vs. 3.6 months; HR = 0.34; 95% CI, 0.25-0.47).

Olaparib also was associated with longer radiographic PFS among the overall population of men with homologous recombination repair-mutated disease, including those with BRCA1/BRCA2, ATM, CDK12 or 11 other mutations (5.8 months vs. 3.5 months; HR = 0.49; 95% CI, 0.38-0.63).

The most common adverse events associated with olaparib vs. abiraterone or enzalutamide included anemia (47% vs.15%), nausea (41% vs. 19%), fatigue and asthenia (41% vs. 32%), decreased appetite (30% vs. 18%) and diarrhea (21% vs. 7%). Grade 3 or worse adverse events observed on the trial included anemia (22% vs. 5%), fatigue and asthenia (3% vs. 5%), vomiting (2% vs. 1%), dyspnea (2% vs. 0%), urinary tract infection (2% vs. 4%), nausea (1% vs. 0%), decreased appetite (1% each), diarrhea (1% vs. 0%) and back pain (1% vs. 2%).

More patients assigned olaparib vs. abiraterone or enzalutamide experienced an adverse event that led to dose interruptions (22% vs. 4%) or treatment discontinuation (16% vs. 9%).

The FDA is expected to make a decision on this application by the second quarter of 2020.

The FDA granted priority review to olaparib for the treatment of men with metastatic castration-resistant prostate cancer and homologous recombination repair gene mutations who progressed on treatment with a new hormonal agent, according to a press release from the agent’s manufacturers.

Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor.

The FDA based its decision, in part, on data from the randomized phase 3 PROfound study presented in September at European Society for Medical Oncology Congress.

The trial met its primary endpoint, based on significantly longer median radiographic PFS among men with BRCA1/BRCA2- or ATM-mutated metastatic castration-resistant prostate cancer assigned olaparib vs. physician’s choice of enzalutamide (Xtandi; Astellas, Pfizer) or abiraterone acetate (Zytiga, Janssen; 7.4 months vs. 3.6 months; HR = 0.34; 95% CI, 0.25-0.47).

Olaparib also was associated with longer radiographic PFS among the overall population of men with homologous recombination repair-mutated disease, including those with BRCA1/BRCA2, ATM, CDK12 or 11 other mutations (5.8 months vs. 3.5 months; HR = 0.49; 95% CI, 0.38-0.63).

The most common adverse events associated with olaparib vs. abiraterone or enzalutamide included anemia (47% vs.15%), nausea (41% vs. 19%), fatigue and asthenia (41% vs. 32%), decreased appetite (30% vs. 18%) and diarrhea (21% vs. 7%). Grade 3 or worse adverse events observed on the trial included anemia (22% vs. 5%), fatigue and asthenia (3% vs. 5%), vomiting (2% vs. 1%), dyspnea (2% vs. 0%), urinary tract infection (2% vs. 4%), nausea (1% vs. 0%), decreased appetite (1% each), diarrhea (1% vs. 0%) and back pain (1% vs. 2%).

More patients assigned olaparib vs. abiraterone or enzalutamide experienced an adverse event that led to dose interruptions (22% vs. 4%) or treatment discontinuation (16% vs. 9%).

The FDA is expected to make a decision on this application by the second quarter of 2020.