When Is Bevacizumab (Avastin) Recommended and What Are the Side Effects?

PARP inhibitors work by blocking an enzymeknown as PARPused by cells to repair damage to their DNA. Without normal functioning PARP, tumor cells will accumulate more and more DNA damage, and eventually die. PARP inhibitors have been shown to be most effective in women with a BRCA mutationabout 20 percent of ovarian cancer patientsbut recent studies show that some PARP inhibitors are effective in ovarian cancer patients who don't have a BRCA mutation.

According to Dr. Oliver Dorigo, director of gynecologic oncology at Stanford University Medical Center, the PARP inhibitor niraparib can benefit a wide range of women with ovarian cancer. "We have trials that have shown niraparib can be beneficial in the maintenance setting [for any ovarian cancer patient]…independent of a BRCA mutation," he told SurvivorNet.

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.

What Is Bevacizumab (Avastin)?

Bevacizumab is often used as part of a maintenance regimen to keep ovarian cancer in remission, as part of treatment during a full-blown recurrence, and also in frontline treatment such as neoadjuvant chemotherapy in combination with olaparib (brand name LYNPARZA). It works by blocking vascular endothelial growth factor (VEGF), a protein that creates tumor-feeding blood vessels. This cuts off the tumor’s blood flow and oxygen supply, stops the tumor from growing, and ultimately kills it. Rather than killing cancer cells themselves, as chemotherapy does, bevacizumab chokes the cells at their roots. If you think about ovarian cancer as weeds growing in a garden, Avastin is like a pesticide.

Combination drug therapies are often more powerful than drugs used separately, but their combined use must also be tested to confirm their effectiveness and approved for such use by the FDA.  For ovarian cancer treatment, olaparib and bevacizumab were found to offer benefits when used in combination, the PAOLA study showed. The study showed there was an improvement in progression-free survival of about six months in women regardless of BRCA mutation, though those with a BRCA mutation had the best results. The group that did not benefit from the drug combination were those whose tumors do not have homologous recombination deficiency (HRD). HRD means that a woman's ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to defeat.  In patients without HRD, adding olaparib to bevacizumab did not improve progression-free survival.

Who Should Consider Using Avastin?

Many women with ovarian cancer can consider bevacizumab (Avastin) as a part of their treatment plan, particularly after a relatively quick recurrence following chemotherapy. These cases are known as "platinum-resistant" cancers, as the primary agent in many chemotherapies used for ovarian cancers is platinum. When tumors recur less than six months after the end of chemotherapy treatment, bevacizumab can be a next step. There have been some convincing trials showing that there's a pretty strong survival benefit for patients with platinum-resistant cancer with the addition of bevacizumab, and most ovarian cancer patients even without a BRCA mutation can benefit from the drug.

Bevacizumab can be used in combination with chemotherapy for women who have recurring ovarian cancer.

Side Effects

One of the major side effects of bevacizumab is hypertension, or high blood pressure, which needs to be monitored very carefully says Dr. Parker. So women being treated with the drug may need to start taking blood pressure medicine. “Bevacizumab can cause issues with [internal] bleeding or clotting, so if someone has a history of blood clot we need to take that into account.” Patients on Avastin should also take note of headaches and blurred vision.

"Other side effects we can see are nephropathy [a disease of the kidneys], so [we look for] protein in the urine, or we can see renal test increase on that drug. We also worry about less common things such as a fistula, which is an abnormal connection between, for example, the bowel and the skin, or if someone’s had a bowel reconnection, getting a defect in that reconnection. So these are all things that you weigh," Dr. Parker says.

One of the most serious side effects is GI perforation: a hole that develops in the stomach or intestine. Symptoms of that would include pain in your abdomen, nausea, vomiting, constipation, or fever. Patients should call a member of their health team right away if they experience any of these symptoms.

Side effects can also include inflammation, dry skin, back pain, nosebleeds, rectal bleeding, watery eyes, and taste changecommon with other cancer drugs too, along with the caution that pregnant or potentially pregnant women should avoid taking it, as should women undergoing surgery.

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