AstraZeneca, Merck Announce Positive Results for Lynpaza Plus Abiraterone

The drug combination reduced the risk of disease progression by 34% versus the standard of care in first-line metastatic castration-resistant prostate cancer, clinical trial results show.

AstraZeneca and Merck have announced positive results from the PROpel phase 3 trial showing that olaparib (Lynpaza, Merck) in combination with abiraterone demonstrated a clinically meaningful and statistically significant improvement in radiographic progressing-free survival (rPFS) versus the standard of care abiraterone as a first line treatment for individuals with metastatic castration resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations.

These results will be presented on February 17 at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Prostate cancer is the second-most-common cancer in male individuals, causing approximately 375,000 deaths in 2020, according to a statement.

Individuals with advanced prostate cancer have a poor prognosis. with the 5-year survival rate low, and approximately half of individuals with mCRPC receive just 1 line of active treatment.

HRR gene mutations occur in approximately 20% to 30% of individuals with mCRPC.

“The results of the PROpel trial, which showed that olaparib in combination with abiraterone significantly delayed disease progression versus abiraterone by more than 8 months, demonstrate the potential for this combination to become a new standard of care option in mCRPC if approved,” Fred Saad, MD, FRCS, professor and chairman of urology and director of genitourinary oncology at the University of Montreal Hospital Center, said in the statement.

In a predefined interim analysis, olaparib in combination with abiraterone reduced the risk of disease progression or death by about 34% compared with abiraterone alone.

Additionally, the median rPFS was 24.8 months for the combination compared with 16.6 months for abiraterone alone.

Furthermore, the results also showed a favorable trend toward improved overall survival (OS) with the drug combination compared with abiraterone. However, the difference did not reach statistical significance at the time of the data cut-off.

The trial will continue to assess OS as a key secondary endpoint.

“Results from the PROpel trial showed that Lynparza in combination with abiraterone plus prednisone reduced the risk of disease progression or death by a third compared to abiraterone plus prednisone in the first-line setting for patients with metastatic castration-resistant prostate cancer, regardless of their biomarker status,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development and chief medical officer at Merck Research Laboratories, said in the statement.

Additional data from efficacy endpoints, such as circulating-tumor-call counts, objective response rate, prostate-specific antigen levels, second progression-free survival, and time to first subsequent therapy, further support the treatment benefits of the combination compared with the single drug in the overall trial population.

The safety and tolerability were in line with that observed in prior clinical trials and the known profiles of the individual medicines.

Additionally, there was no increase in the rate of discontinuation of abiraterone in individuals treated with the combination and no detrimental effects on health-related quality of life versus those treated with the single drug.

Reference

Lynparza plus abiraterone reduced risk of disease progression by 34% vs. standard-of-care in 1st-line metastatic castration-resistant prostate cancer. AstraZeneca. February 14, 2022. Accessed February 16, 2022. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/lynparza-combo-delays-progression-risk-in-prostate-cancer.html