In a nutshell
This study evaluated the effects of olaparib (Lynparza) on pain and the health-related quality of life (HR-QoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) with mutations (genetic abnormalities) in DNA repair genes. The data showed that treatment with olaparib was associated with a reduction in pain and improvement in HR-QoL compared with physician’s choice of hormone therapy in these patients.
mCRPC is an aggressive form of PC that has spread beyond the prostate gland and is no longer responsive to hormonal therapy such as androgen-deprivation therapy (ADT). ADT reduces the production of androgens (male sex hormones such as testosterone). Reducing these androgens prevents cancer cell growth.
BRCA1 and BRCA2 gene mutations (abnormalities) can be found in many patients with breast, ovarian cancer, and prostate cancer. BRCA1/BRCA2 genes block the rapid and uncontrolled growth of cells, therefore the formation of tumors. ATM is a gene that functions as a DNA-damage checkpoint. Loss of function of these genes can lead to tumor formation. Targeted therapy is an option for these patients.
Olaparib is a targeted therapy that blocks a protein called PARP, which helps damaged cells to repair themselves. Therefore, PARP inhibitors keep cancer cells from repairing themselves which eventually causes them to die. BRCA1 and BRCA2 mutated cancers have been shown to be responsive to PARP-inhibitors like olaparib. Previously it was shown that olaparib improved the survival outcomes in patients with mCRPC, particularly in patients with BRCA1, BRCA2, or ATM mutations. However, the effects of olaparib on pain and the HR-QoL in patients with mCRPC with mutations in DNA repair genes are still unknown.
Methods & findings
This study involved a total of 245 men with mCRPC who all had mutations in DNA repair genes. All patients 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 included 162 patients who had mutations in the BRCA1, BRCA2, or ATM genes. Group B included 83 patients who had mutations in other DNA repair genes. Both groups were randomly assigned into 2 subgroups. One subgroup in each group received olaparib and the other subgroup received prednisone (Deltasone; a steroid hormone) with either enzalutamide or abiraterone (control group). The average follow-up time was 6.2 months in the olaparib group and 3.5 months in the control group. The pain and quality of life related to the patients' health were measured by patient questionnaires.
The average time to pain progression was not reached in the olaparib group (exceeded the average follow-up time) compared to 9.92 months in the control group. The average time to pain progression was 56% longer in the olaparib group compared to the control group.
The average time to progression of pain severity was not reached in either of the treatment groups. After 12 months, 81.7% of patients in the olaparib group remained free from pain severity progression compared to 61.9% of patients in the control group.
In patients who had not used opiates (strong pain medications) since the start of treatment, the average time to first opiate use for cancer-related pain was significantly longer in the olaparib group (18 months) than in the control group (7.5 months).
Patients who received olaparib were 8.32 times more likely to experience a clinically meaningful improvement in HRQoL than those treated with enzalutamide or abiraterone.
The bottom line
This study concluded that treatment with olaparib was associated with a reduction in pain and improvement in HR-QoL compared with physician’s choice of hormone therapy in patients with mCRPC with mutations in DNA repair genes.
The fine print
This study was funded by AstraZeneca and Merck Sharp & Dohme., the manufacturers of olaparib. The patients knew which treatment they were getting. This might have influenced how they responded to questionnaires.
Published By :
The Lancet. Oncology
Feb 11, 2022