The New Combination Therapy
- A new two-drug therapy was just approved by the FDA as maintenance therapy ovarian cancer
- Maintenance therapy is intended to prolong cancer remissions
- The drug combination consists of olaparib (a PARP inhibitor drug that stops cancer cells from repairing their DNA) and bevacizumab (brand name Avastin, a targeted drug that stops the formation of new blood vessels and starves cancer of nutrients)
- Experts say this combination is not necessarily more effective than a PARP inhibitor alone for all women
In May 2020 the Food and Drug Administration approved a new combination of drugs as maintenance therapy for ovarian cancer. The two drugs are olaparib plus bevacizumab. Olaparib (brand name Lynparza) is a PARP inhibitor, a drug that acts to kill cancer cells by preventing them from repairing damaged genetic material. Bevacizumab (brand name Avastin) is an anti-angiogenic drug, which works by preventing the formation of new blood vessels, starving cancer cells of nutrients.Read More
The FDA based approval largely on a study done in Europe known as PAOLA-1 . It looked at patients who receiived chemotherapy with bevacizumab, then either continued the bevacizumab along with a placebo, or with olaparib. “The study looked at the difference in progression-free survival between the two groups,” explains Dr. Ramez Eskander, a gynecologic oncologist with the University of Calfornia, San Diego. What the study found was that in women with specific gene mutations or biomarkers there was an incredible benefit to the combination therapy.
“That was true in the population with BRCA mutations, whether it was an inherited mutation [called a germline mutation] or a mutation in the tumor [called a somatic mutation],” says Dr. Eskander. The benefit to the combination therapy was also found in patients with homologous recombination deficiency, known as HRD, which is a genetic factor that indicates ovarian cancer cells cannot easily repair their own damaged genetic material.
Another important statistic from a clinical trial like this is called the hazard ratio, which quantifies the reduction in the risk of the disease recurring. In the PAOLA-1 trial, the hazard ratio in the population of women with either a BRCA mutation or HRD “was about 0.3 or 0.4, meaning a 60 to 70 percent reduction in the risk of the cancer coming back with the incorporation of these maintenance strategies. So we are incredibly excited,” enthuses Dr. Eskander.
More Options for Ovarian Cancer Patients
The approval for the new combination therapy comes on the heels of another recent approval in April for niraparib (brand name Zejula) another PARP inhibitor, as maintenance treatment for ovarian cancer. While initially women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, newer research has shown that women with the BRCA gene mutation (and indeed almost all women), can consider using PARP inhibitors throughout their treatment. “I’m thrilled for my patients who now have an opportunity for maintenance niraparib or maintenance olaparib plus bevacizumab,” says Dr. Eskander.
Along with these exciting developments, there are more in the pipeline for ovarian cancer patients. Dr. Eskander says patients are very eager to see immunotherapy treatments developed for ovarian cancer. “And there are several frontline clinical trials that are looking at different combinations with immunotherapy. This is just the beginning,” he says. “We anticipate over the next year, to two, to three, there is going to be continued evolution in this space and we’re going to hopefully have alternate opportunities and treatment strategies for our patients.”
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.”