PARP Inhibitors Bring Encouraging Results

The last few years have been encouraging for the physicians, patients, and pharmaceutical companies battling ovarian cancer. In large part, this optimism stems from the development of poly (ADP-ribose) polymerase (PARP) inhibitors, which in recent years were approved as a targeted therapy treatment, and which have subsequently led to longer progression-free survival rates.

How PARP Inhibitors Work

PARP inhibitors are a kind of therapy that inhibit targeted proteins (PARP proteins) in cancer cells. The PARP proteins—when allowed to function—repair single-strand breaks in cancer cell DNA. By blocking these PARP proteins, the PARP inhibitors cause cell death amongst the cancerous cells. There have been several recent and groundbreaking trials that have shown the efficacy of PARP inhibitors in the management of platinum-sensitive recurrent ovarian cancer. The physicians overseeing these trials, the patients participating in them, and the companies that have provided these medications have all been trailblazers for PARP inhibitor use.

In December 2014, the FDA approved olaparib (trade name Lynparza) as a treatment for germline mutated BRCA advanced ovarian cancer (gBRCAm) in patients who have been treated with three or more prior lines of chemotherapy. It was the first time the FDA had approved new therapy for ovarian cancer in several years.

Ovarian cancer was the first cancer to have demonstrated benefits from PARP inhibitor treatment.

There have been several encouraging PARP inhibitors approved for marketing by the FDA since the initial approval of olaparib in 2014, including: niraparib (Zejula) in 2017, for epithelial ovarian, fallopian tube, and primary peritoneal cancer; rucaparib (Rubraca) in 2016, for previously treated BRCA-mutant ovarian cancer; and talazoparib (Talzenna) in 2018, for breast cancer with germline BRCA mutations. Other PARP inhibitors are currently being assessed for market approval.

The Future of PARP Inhibitor Treatment

The next steps in PARP inhibitor targeted therapy are refinement and expansion.

Firstly, we need to find out what the impact of PARP inhibitor treatment is on women with newly diagnosed ovarian cancer, which could greatly improve overall survival rates for patients. That means we need to undertake new clinical trials where we take the drugs that are currently being used actively in the recurrent setting and put them in the upfront setting. That would potentially allow us to make a meaningful impact on the treatment of the cancer starting at initial diagnosis.

Right now, PARP inhibitor treatment is utilized for patients with BRCA mutations only—a minority subset of the ovarian cancer population (about 15% of all diagnoses). But PARP inhibitors may also benefits those without BRCA mutations, a hope that may be revealed in forthcoming research.

We also need to look at PARP inhibitor combinations and try to figure out how to expand the usage and efficacy. That means exploring ways to make PARP inhibitors work better in patients who have shown more positive responses to single agents.

Then there’s the matter of possible resistance to the PARP inhibitors. Sometimes patients will become resistant to PARP inhibitors. How should we address these instances medically? We need to understand how best to use other agents and methods to neutralize the potential for resistances. Fortunately, there are a lot of labs working on the answer to that question now, in addition to conducting further clinical trials.

250,000 American Women Currently Have Ovarian Cancer

There are about 250,000 women currently living with an ovarian cancer diagnosis in the United States alone. That’s a large population of women. But overall survival of our patients is improving, and women are living longer with the disease than they ever did before. Now is a time for optimism. We need to continue to develop clinical trials to find new ways for prolonging their lives even more.

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