ESMO 2022 Preview: Metastatic Castration Resistant Prostate Cancer (mCRPC)

Lynparza, the first PARP inhibitor to enter the first-line metastatic castration resistant Prostate Cancer (mCRPC) Setting

The current standard treatment for patients with Castration Resistant Prostate Cancer (CRPC) includes Androgen Deprivation therapies (ADTs), chemotherapy, Zytiga (abiraterone acetate), Xtandi (enzalutamide), PARP inhibitors including Lynparza (olaparib), and Rubraca (rucaparib), along with Xofigo (radium-223) (for bone metastases). Two PARP inhibitors, rucaparib, and olaparib received FDA approval in May 2020 for use in mCRPC harboring selected HRR aberrations after progression on at least one NAA therapy (olaparib) and at least one NAA and one chemotherapy (rucaparib). At present, the use of these agents is contingent upon the presence of aberrations in the HRR gene as identified on a commercial assay. Moreover, talazoparib (Talzenna, Pfizer) and niraparib (Zejula, Janssen) are also being investigated in combination with an AR-directed therapy for first-line treatment of mCRPC, similar to olaparib and rucaparib

Castration Resistant Prostate Cancer (CRPC) Upcoming Abstracts summarized:

Insights:

In the current CRPC market, Lynparza (olaparib) is the first and best-in-class oral poly ADP-PARP inhibitor, and the first targeted treatment to block DDR in tumors harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. AstraZeneca has a global strategic oncology collaboration with Merck to co-develop and co-commercialize Lynparza. Currently, there is a critical unmet need among patients diagnosed with mCRPC, where the prognosis remains poor, and treatment options are limited. There is a much-needed treatment option in the first-line mCRPC setting, where olaparib plus abiraterone is also being evaluated.

Recently in August 2022, the FDA accepted the Submission of Supplemental New Drug Application for LYNPARZA (olaparib) in Combination with Abiraterone and Prednisone or Prednisolone for Patients with mCRPC and Granted Priority Review. The FDA has also set a Prescription Drug User Fee Act (PDUFA), or target action, date in the fourth quarter of 2022. Additionally, it is also the first PARP inhibitor to demonstrate clinical benefit in radiographic progression-free survival in combination with a new hormonal agent with or without homologous recombination repair gene mutations. With the critical unmet need, if approved, LYNPARZA with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with mCRPC in first-line setting.

Apart from that, Orion Pharma is also presenting the preliminary Phase II results of the CYPIDES study of ODM-208 in mCRPC patients. The company is evaluating this trial in collaboration with Merck for the treatment of patients with mCRPC. Moreover, ODM-208 has potential efficacy for those cancers that have become resistant to the standard hormonal treatments, giving it a reason to widen its horizon in breast cancer treatment as well. Therefore, it will be much awaited to look forward to the results.