AstraZeneca and Merck Announce Positive Phase III PAOLA-1 Trial Results for Lynparza in Combination with Bevacizumab as First-Line Maintenance Therapy in Advanced Ovarian Cancer

August 15, 2019 /BioValleyBIOON/ -AstraZeneca(AstraZeneca) and its partner Merck & Co. recently jointly announced positive results from the PAOLA-1 Phase III clinical study evaluating Lynparza (olaparib, trade name: Lynparza; generic name: olaparib tablets), a targeted anticancer drug, as first-line maintenance therapy for advanced ovarian cancer.

This is a randomized, double-blind study evaluating the efficacy and safety of Lynparza in combination with the standard-of-care (SoC) agent bevacizumab versus bevacizumab monotherapy as first-line maintenance treatment in women with newly diagnosed advanced (FIGO Stage III and IV) high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved a complete or partial response to first-line platinum-based chemotherapy combined with bevacizumab, regardless of BRCA status.

The results showed that in the intent-to-treat (ITT, i.e., all randomized patients) population, patients receiving Lynparza plus bevacizumab combination therapy had a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with those receiving bevacizumab monotherapy, indicating a significant delay in time to disease progression or death. These results, includingBiomarkersResults of the Subgroup Analysis Will Be Presented at the Upcoming MedicalConferencepublished above. The safety and tolerability observed in the study were generally consistent with the known profiles of each drug.

It is worth noting that the PAOLA-1 study is the second Phase III trial to demonstrate positive results for Lynparza as first-line treatment for advanced ovarian cancer. In another previously reported pivotal Phase III study, SOLO-1, among patients with BRCA-mutated (BRCAm) advanced ovarian cancer who achieved response after first-line platinum-based chemotherapy, Lynparza as first-line maintenance therapy resulted in statistically and clinically significant improvement in progression-free survival (PFS) compared with placebo, reducing the risk of disease progression or death by 70% (HR=0.30 [95% CI=0.23–0.41], p<0.001). After 41 months of follow-up, the median PFS had not been reached in the Lynparza group, whereas it was 13.8 months in the placebo group. At 36 months, 60.4% of patients in the Lynparza group remained free from disease progression, compared with 26.9% in the placebo group.

Jose Baselga, Executive Vice President of Oncology R&D at AstraZeneca, stated, “The positive results from the PAOLA-1 study demonstrate a clear potential benefit of adding Lynparza to standard bevacizumab therapy in patients with advanced ovarian cancer. Following the positive outcomes of the SOLO-1 study in women with BRCA mutations, PAOLA-1 marks another positive Phase III trial for Lynparza as first-line maintenance treatment in women with advanced ovarian cancer. We look forward to discussing these results with global health authorities as soon as possible.”

Roy Baynes, Senior Vice President of Merck Research Laboratories and Global Head of Clinical Development, as well as Chief Medical Officer, stated: “The PAOLA-1 study reflects MSD and AstraZeneca’s continued commitment to improving clinical outcomes for women with advanced ovarian cancer. In this collaborative group trial sponsored by ARCAGY Research, the addition of Lynparza to the standard of care for maintenance therapy was evaluated in a setting representative of real-world clinical practice. By studying Lynparza in a broader patient population, we have gained insights into how it can help more patients with advanced ovarian cancer in the future.”

Ovarian cancer is the eighth most common cause of cancer-related deaths among women worldwide. In 2018, there were nearly 300,000 newly diagnosed cases of ovarian cancer and approximately 185,000 deaths. Most women are diagnosed with advanced-stage (Stage III or IV) ovarian cancer, with a 5-year survival rate of approximately 30%. For newDiagnosisIn advanced ovarian cancer, the primary treatment goals are to delay disease progression as much as possible, maintain patients’ quality of life, and achieve complete remission or cure.

Lynparza is a first-in-class, oral poly(ADP-ribose) polymerase (PARP) inhibitor that selectively kills cancer cells by exploiting defects in the tumor DNA damage repair (DDR) pathway. This mechanism of action enables Lynparza to treat a broad range of cancers with DNA damage repair deficiencies.Tumorpotential.

Lynparza is the first PARP inhibitor launched globally, first approved in the United States in December 2014.FDAApproved. To date, the drug has been approved in 64 countries worldwide for maintenance treatment of platinum-sensitive recurrent ovarian cancer (regardless of BRCA status). In the United States, the European Union, Japan, and several other countries, it is approved as first-line maintenance therapy for advanced ovarian cancer with BRCA mutations (BRCAm) in patients who have achieved response following platinum-based chemotherapy. Additionally, it has been approved in 43 countries, including the United States and Japan, for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy.Breast Cancer, in the European Union, this indication includes locally advanced breast cancer. Currently, Lynparza for the treatment of ovarian cancer, breast cancer, and pancreatic cancer is under review in other jurisdictions.

AstraZeneca and MSD entered into a global strategic collaboration in oncology in July 2017 to jointly develop and commercialize Lynparza and another MEK inhibitor, selumetinib, for the treatment of various types of tumors. Within the class of PARP inhibitors, Lynparza has the broadest and most advancedClinical TrialDevelopment project. Currently, the two parties are collaborating to investigate Lynparza as a monotherapy and in combination regimens for a broad range ofTumortherapeutic potential.

In the Chinese market, Lynparza (Lipuzhuo) was approved in August 2018 for maintenance treatment of platinum-sensitive recurrent ovarian cancer. Lynparza is the first targeted therapy approved for the treatment of ovarian cancer in China, marking the entry of ovarian cancer treatment in China into the era of PARP inhibitors. (Bioon.com)

Original Source:AstraZeneca Website