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LYNPARZA® (olaparib) Reduced the Risk of Death by 31% in BRCA1/2 or ATM-mutated Metastatic Castration-Resistant Prostate Cancer in Phase III Profound Trial

Published: 2020-09-20 16:30:00 ET

LYNPARZA is the only PARP inhibitor to demonstrate overall survival in metastatic castration-resistant prostate cancer

WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced final results from the Phase III PROfound trial that showed LYNPARZA (olaparib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus enzalutamide or abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 or ATM gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations. Patients had progressed on prior treatment with new hormonal agent (NHA) treatments (i.e., enzalutamide and abiraterone).

Prostate cancer is the second-most common type of cancer in men. An estimated 191,930 men in the United States will be diagnosed with prostate cancer in 2020. Approximately 20-30% of men with mCRPC have an HRR gene mutation.

In the key secondary endpoint of OS, LYNPARZA reduced the risk of death in patients with BRCA1, BRCA2, ATM mutations by 31% versus enzalutamide or abiraterone (based on a hazard ratio [HR] of 0.69; 95% confidence interval [CI] 0.50-0.97; p=0.0175). Median OS was 19.1 months for LYNPARZA versus 14.7 months for enzalutamide or abiraterone, despite 66% of men on NHA treatments had crossed over to receive treatment with LYNPARZA following disease progression.

An exploratory analysis also showed a non-statistically significant improvement in OS in the overall trial population of men with HRR gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRRm genes), reducing the risk of death by 21% with LYNPARZA versus enzalutamide or abiraterone (based on a HR of 0.79; 95% CI 0.61-1.03). Median OS was 17.3 months versus 14.0 months for enzalutamide or abiraterone.

Johann de Bono, one of the principal investigators of the PROfound trial, Head of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, said: “LYNPARZA has demonstrated significant clinical benefit across key endpoints in PROfound and the final overall survival results reinforce its potential to change the treatment standard for certain men with metastatic castration-resistant prostate cancer. The PROfound trial shows that LYNPARZA can play an important role in this new era of precision medicine in prostate cancer, bringing a targeted therapy at a molecular level to patients with a historically poor prognosis and few treatment options.”

José Baselga, Executive Vice President, Oncology R&D, said: “These results help to transform the treatment landscape for certain men with metastatic castration-resistant prostate cancer, where overall survival has been very difficult to achieve. LYNPARZA is the only PARP inhibitor to demonstrate overall survival versus enzalutamide or abiraterone for men with BRCA or ATM mutations. We look forward to continuing to bring LYNPARZA to these patients around the world.”

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck, said: “The PROfound trial is the first positive Phase III trial using molecular biomarker testing to help identify treatment options for certain men with metastatic castration-resistant prostate cancer. These results further underpin the importance of genomic testing for HRR gene mutations to identify this at-risk patient population and help physicians make treatment decisions. These results demonstrate the potential of LYNPARZA for metastatic castration-resistant prostate cancer patients with certain HRR mutations.”

Final OS results from the PROfound trial were presented on Sunday, September 20 during the Presidential Symposium at the 2020 European Society of Medical Oncology virtual congress, and published simultaneously in The New England Journal of Medicine.

Summary of OS results OS data cut-off date was March 20, 2020
	Men with BRCA1/2 and ATM mutations		Overall population (HRRm - BRCA1/2, ATM and 12 other genes)
	LYNPARZA n=162	enzalutamide and abiraterone n=83	LYNPARZA n=256	enzalutamide and abiraterone n=131
Median, months	19.1	14.7	17.3	14.0
Hazard ratio (95% CI)	0.69 (0.50, 0.97)		0.79 (0.61, 1.03)
p-value	0.0175		n/a
Kaplan-Meier estimates of OS
6-months (%)	91	84	92	83
12-months (%)	73	61	67	56
18-months (%)	54	42	47	39
Median follow-up, months	21.9	21.0	20.7	20.5

The most common adverse events (AEs) ≥20% were anemia (50%), nausea (43%), fatigue/asthenia (42%), decreased appetite (31%), diarrhea (21%) and vomiting (20%). The most common ≥ grade 3 AEs were anemia (23%), nausea (2%), fatigue/asthenia (3%), decreased appetite (2%) and diarrhea (1%). Twenty percent of patients on LYNPARZA discontinued treatment due to AEs.

The Phase III PROfound trial had met its primary endpoint in August 2019, showing LYNPARZA significantly improved radiographic progression-free survival (rPFS) in men with BRCA1/2 or ATM genes, and had met a key secondary endpoint of rPFS in the overall HRRm population, which formed the basis of the US approval in May 2020. Regulatory reviews are ongoing in the EU and other countries.

AstraZeneca and Merck are exploring additional trials in metastatic prostate cancer including the ongoing Phase III PROpel trial testing LYNPARZA as a 1st-line medicine for patients with mCRPC in combination with abiraterone versus abiraterone alone. Data is anticipated in the second half of 2021.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in

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All statements made via social media sites sponsored or maintained by Enhanced Investments and its affiliates are for informational purposes only and do not constitute a comprehensive description of Enhanced Investments' investment advisory services.
Certain investments are not suitable for all investors. Before investing, consider your investment objectives and applicable fees. The rate of return on investments can vary widely over time, especially for long term investments. Investment losses are possible, including the potential loss of all amounts invested. Information provided by Enhanced Investments is for informational and general educational purposes only and is not investment or financial advice.