Lynparza Improves Quality of Life in Men with Metastatic Prostate Cancer

The PARP inhibitor Lynparza (olaparib), a type of drug that is usually used for the treatment of women with ovarian cancer, has also been studied in men with prostate cancer. The results of the PROfound clinical trial were recently presented at the 2020 ASCO annual meeting by Antoine Thiery-Vuillemin, MD, PhD, Centre Hospitalier de Besançon, France.

According to Dr. Thiery-Vuillemin, the use of olaparib significantly improved the quality of life of men with a metastatic (spreading) castration-resistant prostate cancer and a homologous recombination repair (HRR) gene mutation. Castration-resistant prostate cancer is the most common type of prostate cancer. HRR gene mutations include genetic alterations in the BRCA1, BRCA2, and/or ATM genes.

Even though the treatment options have increased for men with metastatic prostate cancer, the 5-year survival rates are still low, and HRR gene mutations occur in about 20% to 30% of patients with metastatic castration-resistant prostate cancer.

The PROfound Clinical Trial

The first results from the PROfound clinical trial showed that olaparib extended the survival of patients with this type of prostate cancer compared with men who received the drugs often used for prostate cancer, Xtandi (enzalutamide) or Zytiga (abiraterone). Based on these results, in May 2020, olaparib was approved by the FDA for use in men with metastatic castration-resistant prostate cancer and HRR gene mutation.

At the ASCO meeting this year, Dr. Thiery-Vuillemin presented the results of patient-reported outcomes that were reported by the study patients themselves about the impact of the drug on their quality of life during the study.

In addition to the main objectives of the study, Dr. Thiery-Vuillemin said, “olaparib also maintains quality of life compared with physician’s choice of enzalutamide or abiraterone. Olaparib was also associated with less deterioration in health-related quality of life functioning over time.”

The study participants were divided into 2 groups—group A included patients with HRR mutation, including BRCA1, BRCA2, or ATM mutations. Group B included patients with gene mutation in any of 12 other genes that were selected by the investigators. All the patients were asked to complete a health-related quality-of-life questionnaire at the beginning of the study, and then every 8 weeks, until their cancer progressed (got worse).

Health-related quality of life was assessed with the Functional Assessment of Cancer Therapy-Prostate questionnaire, which is made up of 5 subscales that include physical well-being, functional well-being, emotional well-being, social well-being, and prostate cancer.

At the beginning of the study, 72% of the patients who received olaparib and 71% of the patients who received the control treatment completed the quality-of-life questionnaire. The total scores on the questionnaire were similar in the 2 treatment groups at the start of the study.

Better Quality of Life with Olaparib

Olaparib was associated with better quality-of-life functioning over time compared with the physician’s choice of other treatments. For all the questionnaire subscales, a decrease in score translated to a worsening of quality of life.

“There was less deterioration in the change from baseline in the olaparib arm versus the control arm,” Dr. Thiery-Vuillemin said. “This difference between arms was statistically, and moreover clinically, significant.” (Statistical significance refers to the reliability of scientific study results, whereas clinical significance is a measure of the actual real-world impact on patients.)

More patients in the olaparib group also showed improvements in the questionnaire total scores and in each subscale score, and a clinically meaningful difference in favor of olaparib was seen in the physical well-being score and in the prostate cancer subscale. Patients in the overall population who received olaparib also maintained better quality of life for a much longer period during treatment.

“Having this type of data allows us to better understand the benefit of olaparib from the patient’s perspective,” said Dr. Thiery-Vuillemin.

“This is key when the disease is metastatic prostate cancer, which is known to produce symptoms like asthenia [weakness] and pain from bone metastases, as these symptoms are well-known to impair health-related quality of life,” Dr. Thiery-Vuillemin added.