February 20, 2019
Olaparib Maintenance Therapy for Newly Diagnosed Advanced Ovarian Cancer: In December 2018, olaparib (Lynparza®) received FDA approval for maintenance treatment of adult women with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Olaparib is a PARP inhibitor initially approved for recurrent, platinum-sensitive BRCA1/2 positive ovarian cancer. In 2017, olaparib received approval for maintenance therapy in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy. The most recent FDA approval extends the indication for maintenance therapy to newly diagnosed patients. A randomized, double-blind, placebo-controlled, multicenter phase 3 trial demonstrated that olaparib as maintenance therapy for newly diagnosed advanced ovarian cancer patients with BRCA-mutation significantly improves PFS after first-line chemotherapy with platinum-based chemotherapy.
Ovarian cancer is denoted “the silent killer” because of the nonspecific signs and symptoms that contribute to the delay in diagnosis. The few patients who present with disease still confined to the ovary will have a 5-year survival rate greater than 90%, but most patients present with advanced disease and have a 5-year survival rate of 10% to 30%.
Ovarian cancer is a sporadic disease with less than 10% of cases of ovarian cancer attributed to heredity. However, a history of two or more first-degree relatives with ovarian cancer increases a woman’s risk of developing ovarian cancer by greater than 50%.
Considerable education efforts have been made to identify patients with the persistence, greater than 2 weeks, of nonspecific presenting symptoms of ovarian cancer including: abdominal pressure/pain, difficulty eating or feeling full quickly, urinary urgency/frequency, change in bowel habits, or unexplained vaginal bleeding.
CA-125 is a nonspecific antigen used as a tumor marker for diagnosis and monitoring epithelial ovarian carcinoma. If CA-125 is positive at the time of diagnosis, changes in CA-125 levels correlate with disease response and progression.
Although most patients will achieve a complete response to initial treatment, more than 50% of patients will have recurrence within the first 2 years. If recurrence occurs less than 6 months after completion of chemotherapy, the tumor is defined to be platinum-resistant. The antitumor activity of second-line chemotherapy regimens is similar, and the choice of treatment for recurrent platinum-resistant ovarian cancer depends on residual toxicities, physician preference, and patient convenience. Participation in a clinical trial is also a reasonable option for these patients.
Ovarian cancer is staged surgically with the International Federation of Gynecology and Obstetrics (FIGO) staging algorithm. Tumor debulking and total abdominal hysterectomy–bilateral oophorectomy surgery are the primary surgical interventions for ovarian cancer. After the completion of the staging and primary surgical treatment, the current standard of care is six cycles of a taxane/platinum-containing chemotherapy regimen.
The interperitoneal (IP) route of chemotherapy administration has significantly improved progression-free and overall survival, but patients must be ...