Lynparza Plus Investigational Alpelisib Is Promising for Epithelial Ovarian Cancer

Lynparza Plus Investigational Alpelisib Is Promising for Epithelial Ovarian Cancer
A combination of Lynparza (olaparib) and the investigational PI3K inhibitor alpelisib is safe for the treatment of recurrent epithelial ovarian cancer and induces at least stable disease in more than 80% of patients, results from a Phase 1 trial show. Importantly, the combination was effective in women without any BRCA mutations and with platinum-resistant cancers, a population that PARP inhibitors such as Lynparza often fail to benefit. The study, “Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial,” was published in the journal The Lancet Oncology. Over the past decade, physicians have been successful in treating advanced ovarian cancer with inhibitors of an enzyme called oral poly (ADP-ribose) polymerase (PARP), which is involved in repairing damage to DNA. Repairing damage to DNA allows the cancer cells to continue to grow. Therefore, PARP inhibitors are effective at stopping cancer growth. To date, three PARP inhibitors are approved for ovarian cancer treatment: Lynparza (by AstraZeneca), Rubraca (rucaparib, by Clovis Oncology), and Zejula (niraparib, by Tesaro, now acquired by GSK). But ovarian cancer cells often acquire new mutations that allow them to regain a functional DNA repair mechanism, leading to PARP inhibitor resistance. Therefore, researchers hypothesize that combining PARP inhibitors with other inhibitors of DNA repair can benefit patients with this disease. The DNA repair process requires the involvement of several different types of enzymes aside from PARP. Hence, there are several strategies that can be used to overcome resistance to PARP inhibitors. A group of drugs known as PI3K inhibitors increase the deficiency in DNA r
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