Dr Rathkopf on the Rationale for Evaluating Niraparib Plus Abiraterone Acetate in HRR+ mCSPC

“In the metastatic castration-resistant [prostate cancer] setting, the combination of niraparib plus abiraterone [acetate] demonstrated improvement in terms of radiographic progression-free survival, so we decided to [evaluate] this [combination] in [patients with] metastatic castration-sensitive prostate cancer in the phase 3 AMPLITUDE study.”

Dana E. Rathkopf, MD, a genitourinary medical oncologist and chair of the Research Council at Memorial Sloan Kettering Cancer Center, discussed the impetus and design of the phase 3 AMPLITUDE trial (NCT04497844), which evaluated the efficacy and safety of niraparib (Zejula) plus abiraterone acetate (Zytiga) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).

Data from the phase 3 study that demonstrated the efficacy of a PARP inhibitor combined with an androgen receptor pathway inhibitor (ARPI) in the mCSPC setting, Rathkopf began. She noted that patients with homologous recombination repair (HRR) mutations often have a worse prognosis. An effort toward identifying therapies—especially targeted therapies—is important to help improve outcomes for patients with prostate cancer, particularly those with metastatic castration-resistant prostate cancer (mCRPC), she explained. Previously, the combination of niraparib and abiraterone acetate demonstrated improvements in terms of radiographic progression-free survival (rPFS) in patients with mCRPC, she added. Therefore, investigators aimed to evaluate the respective regimen in patients with mCSPC in the phase 3 study, she asserted.

Of note, patients on the placebo-controlled, blinded study were randomly assigned to receive niraparib plus abiraterone acetate and androgen deprivation therapy (ADT; n = 348) or placebo plus abiraterone acetate and ADT (n = 348). Furthermore, patients included had mCSPC; an alteration in at least 1 HRR eligible gene, including BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, and RAD54L; and an ECOG performance status of 0 to 2. Eligible patients were stratified based on prior docetaxel, volume of disease, and the type of HRR mutation, she noted. The primary end point was rPFS, she concluded.