The Future of Ovarian Cancer Treatment

Until fairly recently, treatment for ovarian cancer was largely a one-size-fits-all approach. Once a woman received a diagnosis, the next steps were surgery and chemotherapy, although not necessarily in that order. And the chemotherapy was almost always a combination of a platinum-based drug (such as cisplatin) and a drug from the taxene family (such as paclitaxel). This duo is still a very important part of ovarian cancer treatment. But it’s no longer the only treatment, prescribed to every woman after diagnosis. “That’s changed now,” says Dr. Ramez Eskander, gynecologic oncologist at the University of California, San Diego. “Now we’re being a little bit more critical about how we’re examining treatment strategies.”

What’s responsible for the change is new data from clinical trials that have looked at genetic differences and other markers in ovarian cancer patients. The key to knowing which women will benefit most from which drugs is to identify the relevant biomarkers. These are specific characteristics that can be measured, and give doctors clues to how effective a drug will be. One biomarker, for example, is a mutation in the BRCA gene, which has been linked to both breast and ovarian cancer.

Recently, for instance, there have been several recent trials that resulted in FDA approvals around a class of drugs called PARP inhibitors for the treatment of ovarian cancer. PARP inhibitors work by preventing damaged DNA in cancer cells from repairing themselves, resulting in the cells’ death.  Women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, however newer research has shown that women with the BRCA gene mutation (and indeed almost all women), can consider using PARP inhibitors throughout their treatment. Most recently, the Food and Drug Administration has approved, niraparib (brand name Zejula), for almost all women regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what’s called front-line treatment.

Other individual genetic characteristics can also provide valuable information. For instance, another exciting biomarker, called homologous recombination deficiency (HRD) has emerged over the last year or two. HRD is a genetic factor that indicates ovarian cancer cells can’t easily repair damaged DNA.

The FDA recently approved another PARP inhibitor,  olaparib (brand name Lynparza), which has been found to have a particular benefit for maintenance therapy when paired with a different drug, bevacizumab (brand name Avastin).  Bevacizumab has a different mechanism from PARP inhibitors. It’s an anti-angiogenic drug, which means it prevents the growth of new blood vessels, thereby starving cancer cells of their nutrients.

When bevacizumab is used in conjunction with olaparib (brand name LYNPARZA) in HRD (Homologous Recombination Deficiency) positive women who show a response to platinum-based chemotherapy, the trial showed an increase in progression-free survival from an average of 17 months to 37 months. “HRD is interesting in that it looks like patients who have this and get treated with a PARP inhibitor have a very pronounced response to the treatment,” says Dr. Eskander, who explains that a recent study (called PAOLA-1) showing this response in women with HRD was partly responsible for the recent FDA approval of olaparib plus bevacizumab.

Most recently, the American Society of Clinical Oncology (ASCO) released new guidelines recommending PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

Ovarian cancer patients should be aware that the new PARP inhibitors, while a promising treatment, also carry risks. Dr. Amanika Kumar of the Mayo Clinic spoke to SurvivorNet and cautioned that women need to speak with their doctor to evaluate the benefit of taking a PARP inhibitor to extend life because there are very real side effects due to the toxicity of the drug. “Patients with HRD (homologous recombination deficiency) have a far better response than those without and those with BRCA mutations even more so. It is on us as clinicians to help patients understand the risks and benefits of treatment. Patients who have no mutation or HRD may choose not to go on maintenance (in fact I recommend they don’t) because there is real toxicity to these meds.”

Just as some women lose more weight with low-carb diets while others do better following a low-fat regime, different women with ovarian cancer respond differently to different treatment regimens. As doctors learn more about these individual differences, they will continue to refine their protocols so that every woman with ovarian cancer receives the regimen that will be most effective for her.

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