Reno, Nevada (UroToday.com) -- AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of LYNPARZA in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated.
The CHMP based its positive opinion on results from the Phase 3 PROpel trial presented at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium and later published in NEJM Evidence.
These results showed LYNPARZA in combination with abiraterone and prednisone or prednisolone reduced the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.54-0.81]; p<0.0001) versus placebo plus abiraterone and prednisone or prednisolone. Median radiographic progression-free survival (rPFS) was 24.8 months for the LYNPARZA plus abiraterone arm versus 16.6 months for the placebo plus abiraterone arm, with or without homologous recombination repair (HRR) gene mutations.
The safety and tolerability of LYNPARZA in combination with abiraterone and prednisone or prednisolone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (≥20%) were anemia (46%), fatigue (37%) and nausea (28%). Grade ≥3 AEs were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and nausea (0.3%). Approximately 14% of patients who received LYNPARZA in combination with abiraterone and prednisone or prednisolone discontinued treatment due to an AE.
Prostate cancer is the most commonly diagnosed cancer in men in Europe, with an estimated 473,000 cases and 108,000 deaths in 2020. Approximately 10-20% of patients with advanced prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will develop metastases at the time of CRPC diagnosis. Patients with advanced prostate cancer have a particularly poor prognosis, and the five-year survival rate remains low.
Noel Clarke, urological surgeon and professor of urological oncology at the Christie/Salford Royal Hospitals and University of Manchester and the PROpel trial joint senior investigator, said, “Patients with mCRPC in the European Union have limited treatment options. This form of advanced prostate cancer has a poor prognosis, and treatment decisions after initial diagnosis are critical. If approved in the European Union for prostate cancer of this type, olaparib in combination with abiraterone will provide a much-needed new treatment option for the many men with this condition.”Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, “With the incidence and mortality of prostate cancer set to double in the coming decades, it is more important than ever that we bring new treatment options to suitable patients at the earliest possible moment in their care. If approved, LYNPARZAin combination with abiraterone and prednisone or prednisolone will represent the first combination of a PARP inhibitor and a new hormonal agent available to patients in the European Union.”
Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, “While prostate cancer has seen many advances in care in recent decades, for those with mCRPC, new treatment options are urgently needed. We are fully committed to bringing LYNPARZAin combination with abiraterone and prednisone or prednisolone to suitable patients in Europe as quickly as possible.”
LYNPARZA in combination with abiraterone and prednisone or prednisolone is undergoing priority review in the U.S. for the treatment of adult patients with mCRPC based on results from the Phase 3 PROpel trial, with a decision expected in Q4 2022.
LYNPARZA monotherapy is approved in the U.S. based on results from the Phase 3 PROfound trial for patients with HRR gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the European Union, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent (NHA).
Source: “Lynparza® (OLAPARIB) in Combination with Abiraterone and Prednisone or Prednisolone Receives Positive Opinion from EU CHMP as Treatment for Certain Patients with Metastatic Castration-Resistant Prostate Cancer.” Merck.com, November 14, 2022.
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ASCO GU 2022: PROpel: Phase III Trial of Olaparib and Abiraterone Versus Placebo and Abiraterone as First-Line Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC)