Dr. Maha Hussain

Olaparib (Lynparza) Targeted Therapy for Metastatic Castration-Resistant Prostate Cancer

Dr. Maha Hussain

Dr. Hussain

MedicalResearch.com Interview with:
Maha Hussain, MD, FACP, FASCO
Genevieve Teuton Professor of MedicineDivision of Hem/Onc
Deputy Director
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

MedicalResearch.com: What is the background for this study?

Response: PROfound is an open-label international Phase III clinical trial which evaluated the efficacy and safety of Olaparib (Lynparza) versus enzalumatide or abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior treatment with NHA treatments (abiraterone and prednisone or enzalutamide) and have a qualifying tumor mutation in BRCA1/2, ATM or one of the other genes involved in the HRR pathway.

The trial design included 2 cohorts; Cohort A included patients with BRCA1,2 or ATM and Cohort 2 included patients with 12 other HRR genes.

MedicalResearch.com: What are the main findings?

Response: The primary endpoint was rPFS in cohort A patients (those with mutations in BRCA1/2 or ATM genes) and then, if Lynparza showed clinical benefit, a formal analysis was performed of the overall trial population of patients in addition to other secondary end points (Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.)

MedicalResearch.com: What should readers take away from your report?

    • Treatment with Olaparib reduced the risk of death by 31% (HR 0.69 95% CI 0.50-0.97) in men with BRCA1/2 or ATM gene mutations vs. those treated with enzalutamide or abiraterone and prednisone, which occurred despite substantial cross-over of control-arm patients to receive Olaparib.
    • Olaparib is the first PARP inhibitor to demonstrate an overall survival in metastatic castration-resistant prostate cancer with HRR mutations.
    • Olaparib also delayed time to pain progression; a critical factor particularly in metastatic castration resistant prostate cancer.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

    • The PROfound trial demonstrated the feasibility and impact of targeted therapy in preselected patient with metastatic castration resistant prostate cancer.
    • Future research should focus on testing rational combination therapies to enhance the antitumor impact,  testing  other targeted therapies that are applicable to this disease, identify new potential relevant pathways and advance effective therapies to earlier disease settings where “clinical ROI” is likely to be even more.

MedicalResearch.com: Is there anything else you would like to add? 

    • To understand the importance of these results, it is important to understand the patient population. Despite advances in treatment for men with metastatic castration-resistant prostate cancer, the disease continues to be very deadly and five-year survival remains low.  Prolonging survival remains a key goal for treating these men.
    • On behalf of all investigators I would like to extend my thanks and gratitude to all patients, their families and all investigators for their volunteering and participation.  Research and collaboration will conquer cancer

COI disclosures are all in NEJM pub.

Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.

Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators.N Engl J Med. 2020 Sep 20. doi: 10.1056/NEJMoa2022485. Online ahead of print.



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Last Updated on October 1, 2020 by Marie Benz MD FAAD