Lynparaza is back in the news again, but this time, according to Cure Today, the FDA approved the drug in combination with Avastin for advanced ovarian cancer to prevent progression of the disease. The newly approved combination targets specific mutations.
As the fifth common cause of cancer deaths in women living in the U.S., approximately 21,000 new cases of ovarian cancer are expected this year. Of that total, approximately 14,000 deaths may occur.
Lynparaza had previously been approved by the FDA in connection with overall survival for men who have advanced prostate cancer.
About BRCA1 and BRCA2 (BReast CAncer Gene)
Both BRCA 1 and 2 genes exist in every human and are usually not the cause of breast cancer. Actually, they help to prevent breast cancer, as they assist in repairing DNA breaks that lead to tumors and cancer. Therefore, BRCA genes are considered to be tumor suppressor genes.
A small percentage of these genes may become damaged (mutated) and lose their ability to repair DNA. People with the BRCA mutation are at greater risk for breast cancer. Their children may also inherit the mutation.
The Phase III PAOLA Trial
FDA approval of Avastin (bevacizumab) and Lynparza (olaparib) was determined by the results of the PAOLA trial. The trial involved 387 patients with advanced endometroid ovarian, peritoneal or fallopian tube cancer.
Patients who were included in the study had previously responded to a powerful platinum-based chemotherapy and had taken Avastin as a single agent.
In addition, eligible patients must have had partial or complete response to previous therapy along with cancer that evidences HRD deficiency as a result of a BRCA gene mutation.
Results of the study confirmed that the combination of Avastin and Lynparaza reduced death or disease progression by forty-one percent. This compared favorably against results of Avastin as a single agent.
The investigators followed patients until disease progression. Progression-free survival was twenty-two months for the combination as compared to sixteen months for Avastin as a single agent.
Lynparza is most effective when administered to patients with tumors that were HRD-positive. This would include patients who were BRCA-positive.
Patients in the HRD/BRCA subgroup receiving the Lynparza combination experienced disease progression at thirty-seven months compared to seventeen months for Avastin alone.
The subgroup who were HRD-positive but without BRCA mutations exhibited twenty-eight months until progression of the disease compared with sixteen months with Avastin.
About Side Effects
Severe side effects were noted in fifty-seven percent of patients in the combination therapy. This compares to fifty-one percent of patients who received Avastin alone.
Side effects leading to dose interruption amounted to fifty-four percent of patients taking the combination, as opposed to twenty-four percent of patients receiving Avastin as a single agent.
Common adverse reactions appearing in over twenty percent of patients receiving the combination therapy were nausea, fatigue, anemia, joint pain, reduced lymphocytes, and high blood pressure.
The developers, Merck and AstraZeneca, have indicated that they are applying for approval by the EU, Japan, and several other countries for Lynarza in combination with Avastin as first-line maintenance therapy for patients diagnosed with advanced ovarian cancer.