In a nutshell
This study assessed whether olaparib (Lynparza) affected progression-free survival (PFS; survival without cancer worsening) in patients with metastatic castration-resistant prostate cancer (mCRPC) and certain genetic mutations (abnormalities). The study found that olaparib improved PFS in these patients.
MCRPC has poor outcomes. MCRPC is a type of cancer that is no longer responsive to androgen (male sex hormones like testosterone) deprivation therapy. Tumors found in mCRPC often have mixed genetic abnormalities. BRCA1 and BRCA2 are genes found in prostate cancer and other types of cancer. They are responsible for repairing DNA when it is damaged. ATM is a gene that functions as a DNA-damage checkpoint. Loss of function of these genes can lead to tumor formation. They are also associated with a sensitivity to PARP inhibition. PARP is a protein that is responsible for DNA repair and other functions within the cell.
Olaparib is a PARP inhibitor that is used in BRCA1 and BRCA2-positive cancers. It was unknown if olaparib would improve the outcomes of patients with mCRPC with genetic abnormalities who have had disease progression after hormonal treatments.
Methods & findings
387 patients with mCRPC and genetic abnormalities were included in this study. All patients had had cancer worsening after hormonal treatment with enzalutamide (Xtandi) or abiraterone (Zytiga). The patients were divided into 2 groups according to the genetic abnormalities in their tumors. Group A (245 patients) had abnormalities of the BRCA1, BRCA2, or ATM genes. Group B (142 patients) had abnormalities in other genes. Both groups were divided into 2 subgroups. One subgroup in each group received olaparib and the other subgroups received prednisone (Deltasone) combined with enzalutamide or abiraterone (control).
Overall, PFS was significantly longer (by 51%) in the olaparib group (5.8 months) when compared to the control group (3.5 months). Patients in the olaparib group were 5.93 times more likely to respond to treatment than the control group. 22% of the olaparib group responded to treatment compared to 4% in the control group.
After 6 months, 85% of the olaparib group pain progression (85%) and 75% of the control group did not have worsening of the pain. The average overall survival (OS) of the olaparib group was 17.5 months compared to 14.3 months in the control group.
In group A, patients treated with olaparib had a 66% higher PFS (7.4 months) compared to the control group (3.6 months). Patients in group A were 20.86 more likely to respond to olaparib treatment compared to the control. 33% of patients treated with olaparib and 2% of controls responded in group A. The average OS was significantly longer in olaparib-treated patients (18.5 months) compared to controls (15.1 months) in group A.
There were more serious side effects reported in the olaparib group (51%) when compared to the control group (38%). Common side effects included anemia, nausea, and fatigue.
The bottom line
This study concluded that olaparib improved the outcomes in patients with mCRPC, particularly in patients with BRXA1, BRCA2, or ATM mutations.
The fine print
This study was supported by AstraZeneca and Merck Sharp & Dohme, the manufacturers of olaparib.
Published By :
The New England Journal of Medicine
Apr 28, 2020
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