Combination Therapy Improves Ovarian Cancer Survival

Avastin was the first drug to receive approval from the Food and Drug Administration (FDA) as a maintenance therapy for ovarian cancer. In combination with other chemotherapy, it helps to prolong the length of time that women live without their cancer growing or spreading.

How PARP Inhibitors Work

The second drug, olaparib (Lynparza), is in a different class of medications, and works differently to defeat cancer cells. Olaparib is a PARP inhibitor. The poly (ADP-ribose) polymerase, or PARP inhibitor drugs are relatively new to cancer care. To date, the FDA has approved three drugs in this class for the treatment of ovarian cancer:

• Olaparib (Lynparza)
• Niraparib (Zejula)
• Rucaparib (Rubraca)

These drugs, which are taken orally, work by preventing cancer cells that have been damaged, such as by chemotherapy, from being able to heal themselves. PARP inhibitors have typically been used as maintenance therapy, to prevent a recurrence of cancer after a woman has already had surgery and traditional chemotherapy. When used this way, PARP inhibitors can potentially prolong remission and prevent disease recurrence for long periods of time maybe even indefinitely.

The FDA also approved the use of PARP inhibitors for the frontline treatment of ovarian cancer, as well as in the maintenance setting. These drugs have typically been most effective in women with certain genetic mutations or markers, including BRCA mutations and homologous recombination deficiency (HRD) a defect in the ability of a cell to repair its DNA.

The American Society of Clinical Oncology (ASCO)  guidelines recommend 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.

Improving Survival Time

The study that evaluated the drug combination of olaparib and bevacizumab was called the PAOLA-1 trial. Women in the trial had all been treated with chemotherapy and bevacizumab, and then they either continued receiving bevacizumab with a placebo (inactive treatment), or with olaparib. The researchers looked at the difference in progression-free survival (how long the women lived without their cancer growing) between the two groups.

The results showed that the greatest benefit was in patients with a BRCA mutation or HRD who received the combination of drugs. In patients with HRD-positive tumors who received bevacizumab plus olaparib, the progression-free survival was just over 37 months, compared to 17.7 months in the group that received the placebo along with bevacizumab. "We are seeing some tremendous progression-free survival benefits, and potentially almost a doubling of the progression-free survival," says Dr. David Engle, a gynecologic oncologist with the Baptist Medical Group in Memphis.

Patients with the BRCA mutation who received both drugs experienced up to a two-year benefit in preventing or delaying their recurrences, "which in our population is huge," says Dr. Engle. "This is something that we are actively seeking for our patients when coming off their first rounds of chemotherapy."

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