This has been a truly historic week, with two new treatment options receiving FDA approval for men with advanced prostate cancer.
On Friday, 5/15/20, the FDA approved rucaparib, a new medication to treat some patients with advanced prostate cancer. Then, on Tuesday, 5/19/20, olaparib was approved by the FDA for certain metastatic prostate cancers that are not responsive to hormone therapy. Rucaparib and olaparib are both “PARP inhibitors,” a class of precision medicines, that are used to treat cancers with specific mutations.
For men with advanced disease, these are two more modern weapons in the fight against advanced prostate cancer, a disease state that, in the past, has had few treatment alternatives. For PCF science, these approvals are an important testament to the value of early foundational work which can bear multiple fruits in the form of new treatments, even many years later. Once again, PCF is proud to have been involved since the beginning, in every stage of the research that lead to this development.
The idea that PARP could be the key to finding treatments for prostate cancer came from a PCF-funded team led by Dr. Karen Knudsen of Thomas Jefferson University. PARP is a protein that is involved in repairing damaged DNA. Dr. Knudsen’s team provided data to prove that PARP is a driver of prostate cancer and that PARP inhibitors can suppress prostate tumor growth and progression.
Then in 2015, the PCF-SU2C International Prostate Cancer Dream Team published a landmark study demonstrating that about a third of mCRPC (metastatic castration-resistant prostate cancer) cases have mutations in certain genes, including about 13% of prostate cancer patients with a BRCA2 mutation (another DNA repair gene) in their tumor. This study, led by Dr. Arul Chinnaiyan, of the University of Michigan, and Dr. Charles Sawyers of Memorial Sloan Kettering Cancer Center, was momentous, providing the motivation to test PARP inhibitors such as olaparib in prostate cancers.
The PCF Dream Team’s findings ignited a race among pharmaceutical companies to develop precision medications for prostate cancer. The PCF Team quickly initiated a Phase 2 clinical trial, led by PCF-funded investigator Dr. Johann de Bono and PCF Young Investigator Dr. Joaquin Mateo, of the Institute of Cancer Research and Royal Marsden NHS Foundation Trust in the UK, which demonstrated that olaparib had anti-tumor activity in mCRPC patients with DDR (DNA Damage Repair) gene alterations. These findings resulted in olaparib receiving an accelerated FDA “Breakthrough Therapy Designation” in prostate cancer.
Rucaparib’s approval is based on results from a phase 2 clinical trial led by PCF Young Investigator Dr. Wassim Abida of Memorial Sloan Kettering Cancer Center, which was presented at the 2019 European Society of Medical Oncology (ESMO) Congress. Olaparib’s approval is based on results from a phase 3 clinical trial (PROfound) led by PCF-funded investigators Dr. Johann de Bono and Dr. Maha Hussain. These practice-changing findings were recently published in the prestigious journal The New England Journal of Medicine.
“This is a leap forward in helping men with mCRPC,” says PCF CEO Dr. Jonathan Simons. “PCF is proud to have funded the patient genomics research that catapulted rucaparib and olaparib into global clinical trials. This kind of DNA-driven precision medicine is the future of treatment and brings us one step closer to our mission to eliminate all death and suffering from prostate cancer.”