Lynparza Reduced the Risk of Cancer Recurrence by 42% in Adjuvant Treatment of Germline BRCA-Mutated High-Risk Early Breast Cancer in OlympiA Phase III Trial

June 09, 2021 /BioonBIOON/ --`AstraZeneca`(AstraZeneca) and Merck & Co. recently announced the targeted anticancer drug Lynparza (Chinese brand name: Lipuzhuo, generic name: olaparib, olaparib tablets) for adjuvant treatment of high-risk BRCA-mutated HER2-negative early-Breast CancerResults from the OlympiA phase III trial (NCT02032823) in patients. Data show that,Compared with placebo, adjuvant treatment with Lynparza resulted in a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS).

It is worth noting that,Lynparza is the first targeted therapy for BRCA mutations to demonstrate clinical benefit in the adjuvant setting.. It is estimated that in 2020, 2.3 million women worldwide wereDiagnosisIn breast cancer, BRCA mutations are identified in approximately 5% of patients. Approximately 55–65% of women with a BRCA1 mutation and about 45% of women with a BRCA2 mutation will develop breast cancer before the age of 70.

AstraZenecaTumorExecutive Vice President of the Business Unit Dave Fredrickson said: “This is the first time any drug targeting BRCA mutations has been shown to have the potential to alter the course of early-stage breast cancer and bring hope for a cure.. By providing a treatment that significantly reduces the risk of breast cancer recurrence in these high-risk patients, we hope Lynparza will set a new benchmark and demonstrate sustained clinical benefit. We are working with regulatory authorities to make Lynparza available to these patients as soon as possible.”

The OlympiA trial was a double-blind, parallel-group, placebo-controlled, multicenter phase 3 study designed to evaluate the efficacy and safety of Lynparza tablets versus placebo as adjuvant therapy in patients with gBRCAm, high-risk, HER2-negative early breast cancer who had completed local therapy and standard neoadjuvant or adjuvant chemotherapy. The primary endpoint of the trial was iDFS, defined as the time from randomization to first treatment failure (local or distant recurrence, new primary cancer, or death from any cause).

In the overall trial population,Compared with placebo, Lynparza reduced the risk of invasive breast cancer recurrence, a second primary cancer, or death by 42% (HR=0.58; 99.5% CI: 0.41-0.82; p<0.0001).。After 3 years, 85.9% of patients in the Lynparza treatment group remained alive and free of invasive breast cancer and second primary cancers, compared with 77.1% in the placebo group.

Additionally, in the overall trial population, Lynparza demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of distant disease-free survival (DDFS) compared with placebo.Lynparza reduced the risk of distant disease recurrence or death by 43% (HR=0.57; 99.5% CI: 0.39-0.83, p<0.0001). At the time of this preliminary data cutoff, fewer deaths were observed among patients treated with Lynparza, but the difference in overall survival (OS) was not statistically significant. The trial will continue to evaluate OS as a secondary endpoint. In this trial, the safety and tolerability of Lynparza were consistent with priorClinical trialconsistent with that observed in.

In February 2021, the Independent Data Monitoring Committee (IDMC) recommended an early interim analysis and reporting for the OlympiA trial. Based on the planned interim analysis, the IDMC concluded that the trial crossed the efficacy boundary for the primary endpoint of iDFS, demonstrating a sustained, clinically meaningful therapeutic benefit of Lynparza compared with placebo.

OlympiA Trial Results

Lynparza is a first-in-class, oral poly (ADP-ribose) polymerase (PARP) inhibitor that exploits defects in tumor DNA damage repair (DDR) pathways to preferentially kill cancer cells. This mechanism of action enables Lynparza to treat a broad range of cancer types with DNA damage repair deficiencies (such as BRCA1 and/or BRCA2 mutations).Tumorpotential.

In July 2017, AstraZeneca and MSD entered into a global strategic collaboration in oncology to jointly develop and commercialize Lynparza and another MEK inhibitor, selumetinib, for the treatment of a wide range of typesTumor, including breast cancer, prostate cancer, and pancreatic cancer.

Lynparza is the world's first globally marketed PARP inhibitor, first approved by the US in December 2014FDAApproved. To date, Lynparza has been approved for seven therapeutic indications: (1) first-line maintenance treatment for adult patients with BRCAm advanced ovarian cancer; (2) first-line maintenance treatment in combination with bevacizumab for adult patients with HRD-positive advanced ovarian cancer; (3) maintenance treatment for adult patients with recurrent ovarian cancer; (4) treatment of adult patients with advanced gBRCAm ovarian cancer; (5) treatment of adult patients with gBRCAm, HER2-negative (HER2-) metastatic breast cancer; (6) first-line maintenance treatment for adult patients with gBRCAm metastatic pancreatic cancer; (7) treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) harboring specific gene mutations.

In China, Lynparza was approved in August 2018 for the maintenance treatment of platinum-sensitive recurrent ovarian cancer. Lynparza is the first targeted drug approved in the Chinese market for ovarian cancer treatment, marking the entry of China's ovarian cancer therapy into the era of PARP inhibitors. In early December 2019, Lynparza received further approval for first-line maintenance treatment in patients with advanced ovarian cancer harboring BRCA mutations. Benefiting from China's strong support for pharmaceutical innovation and the accelerated approval process for clinically urgent new drugs, Lynparza became the first PARP inhibitor approved in China for first-line maintenance therapy of ovarian cancer. On November 28, 2019, Lynparza was included in the National Reimbursement Drug List. (Bioon.com)

Original Source:Lynparza reduced the risk of cancer recurrence by 42% in the adjuvant treatment of patients with germline BRCA-mutated high-risk early breast cancer in OlympiA Phase III trial