Improved outcome for prostate cancer patients in Phase III PROpel trial

PROpel was a randomised, double-blind Phase III trial testing AstraZeneca and Merck’s Lynparza (Olaparib) in combination with abiraterone plus prednisone versus standard-of-care abiraterone plus prednisone as a first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombinant repair (HRR) gene mutations.

Following interim reports from AstraZeneca last September that indicated a trend towards improved radiographic progression-free survival (rPFS) and overall survival (OS), the final results from the full trial confirm these improved statistics.

As previously reported, in the Phase III PROpel trial, Lynparza in combination with abiraterone plus prednisone (n=399) reduced the risk of disease progression or death by 34 percent (HR=0.66 [95 percent CI, 0.54-0.81]; p<0.0001) versus abiraterone plus prednisone and placebo (n=397). Median rPFS was 24.8 months for LYNPARZA plus abiraterone versus 16.6 months for abiraterone.

The most common adverse events (AEs; ≥20 percent) for Lynparza plus abiraterone were anaemia (46 percent), fatigue (37 percent) and nausea (28 percent). Grade ≥3 AEs were anaemia, hypertension, urinary tract infection, fatigue, decreased appetite, vomiting, back pain, diarrhoea and nausea. Approximately 14 percent of patients who received Lynparza in combination with abiraterone discontinued treatment due to an AE.

Cristian Massacesi, chief medical officer and oncology chief development officer, AstraZeneca, reflected: “These data demonstrate that the combination of Lynparza with abiraterone and prednisone afforded patients a median radiographic progression-free survival of over two years, regardless of biomarker status. If approved, the combination will offer patients with and without HRR gene mutations a new treatment option.”

Commenting on the positive benefits of the drug combination for men with mCRPC, Dr Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, explained: “Publication of the PROpel data in NEJM Evidence reflects the benefit seen with the combination of Lynparza plus abiraterone and prednisone in the first-line setting of mCRPC, and we are pleased that these data have been selected for one of the first issues of this new journal.”