Drugs targeting poly (ADP-ribose) polymerase (PARP) are helping patients battle back more effectively against cancer. An enzyme, PARP helps repair damaged DNA in cells, and while that’s a good thing in healthy people, it can be bad news for cancer patients. To prevent PARP from repairing DNA breaks in cancer cells, AstraZeneca developed Lynparza, a PARP inhibitor (PARPi) that secured approval in 2014 for use in advanced ovarian cancer treatment. The five-year survival rate in ovarian cancer is 92% when it’s caught early. However, it’s only 17% for stage IV ovarian cancer patients.
Lynparza’s advanced ovarian cancer approval was supported by trials showing that 34% of patients responded to it for an average of 7.9 months. At first, it was only approved for patients who’d seen their disease return following three or more prior treatments, but its approval was expanded in August 2017 to include its use as a maintenance therapy. When used as a maintenance therapy, Lynparza reduced disease progression or death by 70% in one trial and by 65% in a second trial. It also improved median progression-free survival and median overall survival.
Lynparza isn’t the only PARPi that’s effective in ovarian cancer, either. Tesaro’s Zejula and Clovis Oncology’s Rubraca have also won FDA approval for use following trials that demonstrated their ability to prevent PARP from repairing DNA-damaged cancer cells.
Although ovarian cancer has been the focus of PARPi’s so far, the FDA-approved Lynparza for use in some breast cancer patients in January. Specifically, Lynparza can help metastatic breast cancer patients with mutations to BRCA, another cell repair gene. Because breast cancer is the most common cancer in the U.S., with 252,710 people newly diagnosed annually, and about 5% to 10% of breast cancer patients have a BRCA mutation, far more people are likely to benefit from PARPi soon. PARPis are also being evaluated for pancreatic cancer, triple-negative breast cancer, and metastatic prostate cancer. If those trials succeed, then PARPi could become some of the most commonly used cancer drugs.
The drug, TAK-700 (Ortoronel) and Phase 3 clinical trials have been described in a blog published on this website on June 3rd, 2011. TAK-700 is an oral, non-steroidal, androgen (e.g. testosterone) synthesis inhibitor. It is being developed by the Takeda Oncology Company affiliated with Millennium. They are sponsoring safety and efficacy clinical trials in men with metastatic prostate cancer who have not had previous chemotherapy or who have had chemotherapy more than two years earlier for early-stage prostate cancer (elm pc004) or metastatic cancer who have received chemotherapy (elm pc005). The trials are evaluating the safety and efficacy of TAK-700 when combined with prednisone as compared with prednisone alone. End points of the study are delay in disease progression and increased survival times.