Lynparza Notches EU Authorization for BRCA-Mutated Metastatic Pancreatic Cancer
By T. Chakraborty, Ph.D.
Merck and AstraZeneca’s drug is now the first PARP inhibitor to be approved for this indication of pancreatic cancer in the EU.
Pancreatic cancer is one of the most fatal forms of cancer with a one-year survival rate of 20% and a five-year survival rate of only 7%. The American Cancer Society estimates that in 2020 alone, approximately 58,000 people will be diagnosed and 47,000 will succumb to the disease. Although pancreatic cancers are rare and account for only 3% of cancer cases, it still registers 7% of cancer-related deaths. Hence, biopharma companies are investing big to identify potent drugs.
On July 8th, Merck and AstraZeneca announced that their Poly-ADP ribose polymerase (PARP) inhibitor, Lynparza has been approved in the European Union (EU) for 1st-line maintenance treatment of germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer patients. This approval is a result of the recommendation by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) following positive results from the Phase 3 POLO trial [1,2]. Last December, Lynparza bagged FDA approval for the same indication in the US.
Mutation in BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are involved in DNA repair and maintaining genetic stability. Mutation in these genes causes cells to divide in an uncontrolled fashion, hence developing cancer. Approximately, 5%-7% of metastatic pancreatic cancer patients harbor mutations in the BRCA gene. PARP is an important protein in the DNA repair mechanism and cancer cells exploit it to divide and metastasize. In recent years PARP has gained considerable importance as a targeted therapy in cancer. Lynparza inhibits PARP by trapping PARP bound to DNA single breaks, thereby leading to double-strand breaks and in turn cell death. The drug is under investigation for a plethora of tumor types that are dependent on DNA damage repair.
POLO, a Phase 3 double-blinded randomized placebo-controlled trial, evaluated the efficacy of Lynparza in 154 patients who were shortlisted from a screen of 3315 subjects. Of them, 92 patients received Lynparza tablets (300mg) twice a day and the remaining 62 received placebo. The median progression-free survival was 7.4 months in patients who received the drug versus 3.8 months in patients who did not. No significant changes were observed between the groups with respect to health-related quality of life. Reportedly, 40% of patients treated with Lynparza had grade 3 or higher adverse events compared to 23% in the placebo group. This study was recently published in the New England Journal of Medicine .
Hedy L. Kindler, Professor at the University of Chicago Medicine, said “Today’s approval opens the door to a new era of biomarker-led care for patients with metastatic pancreatic cancer in the EU, which has the highest incidence of any region globally. Lynparza now provides clinicians with a targeted, well-tolerated treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, further added “Patients with metastatic pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and few treatment advances have been made over the last few decades. In the POLO trial, Lynparza nearly doubled median progression-free survival versus placebo after 1st-line chemotherapy for patients with germline BRCA-mutated metastatic pancreatic cancer. This approval underscores the importance of testing all patients for germline BRCA mutations at the time of diagnosis, as it will help inform personalized treatment options for patients in the EU” .
Other PARP Inhibitors
The major competitors in the market are GlaxoSmithKline’s Zejula, Pfizer’s Talzenna, and Clovis Oncology’s Rubraca which have been FDA approved for the treatment of ovarian, breast and prostate cancer respectively. Abbvie’s Veliparib (ABT-888) is currently evaluated in trials to treat pancreatic cancer, non-small cell lung cancer, BRCA breast cancer, and ovarian cancer. With multiple pharmaceutical giants investing in PARP inhibitors as potential treatments for various types of cancer and other diseases, the field is rapidly advancing .
Editor: Rajaneesh K. Gopinath, Ph.D.
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