AstraZeneca and Merck Jointly Release the Results of the Phase 3 Clinical Trial of Olaparib

Recently, AstraZeneca (AstraZeneca) and Merck & Co. (MSD) jointly announced the results of the Phase 3 PROpel clinical trial of its PARP inhibitor olaparib (Lynparza), published in NEJM Evidence, a subsidiary of the New England Journal of Medicine. superior. The results of this trial showed that when olaparib was used in combination with standard therapy, compared with standard therapy alone, radiographic progression-free survival (rPFS) was significantly improved.

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men will be diagnosed with prostate cancer, and about 375,000 people will die from the disease globally. At diagnosis, most men have localized prostate cancer, which can be treated with surgery or radiation. Metastatic prostate cancer develops when the disease metastasizes or spreads. The growth of prostate cancer cells is androgen-dependent, so patients with metastatic prostate cancer are initially sensitive to androgen deprivation therapy (ADT) therapy. Patients with progressive disease after persistent ADT develop metastatic castration-resistant prostate cancer (mCRPC).

Olaparib targets the DNA Damage Repair Response (DDR) pathway and uses the principle of "synthetic lethality" to kill cancer cells while reducing the impact on healthy cells. Olaparib is approved in the United States for use in mCRPC patients with homologous recombination repair mutations (including BRCA and other homologous recombination repair mutations) who have been treated with the androgen receptor antagonist enzalutamide or abiraterone.

PROpel is a randomized, double-blind Phase 3 clinical trial with a primary endpoint of rPFS. Trial results showed that when olaparib was combined with abiraterone and prednisone (n=399), compared with placebo and the combined results of the two drugs (n=397), there was a 34% reduction in Risk of disease progression or death (HR=0.66, 95% CI: 0.54-0.81, P<0.0001). Median rPFS was 24.8 months for the former treatment combination and 16.6 months for the latter.

The most common (≥20%) adverse reactions with olaparib concomitant with abiraterone and prednisone were anemia (46%), fatigue (37%), and vomiting (28%). The adverse reactions of grade 3 or above were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and vomiting (0.3%). About 14% of patients receiving concomitant olaparib discontinued treatment because of adverse reactions.

"PROpel's data published in NEJM Evidence reflect the benefits of combining olaparib with abiraterone and prednisone as first-line therapy for patients with mCRPC, and we are delighted that these data have been selected as one of the first issues of this new journal." said Dr. Eliav Barr, head of global clinical development and chief medical officer at Merck Laboratories.