Olaparib received FDA approval for stage 4. or recurrent ovarian cancer treatment

On 17 August 2017, the United States Food and Drug Administration, FDA, approved maintenance treatment for adult patients with recurrent ovarian, fallopian tube or peritoneal (abdominal lining) cancer who had previously had a complete or partial response to platinum-based chemotherapy, using olaparib tablets (Lynparza).

The fallopian tubes are small tubes that begin adjacent to the right and left ovaries and end at the upper lateral corners on either side of the womb (uterus).

The FDA had previously, in 2014, approved olaparib capsules to treat patients who had received three or more lines of chemotherapy and had an inherited BRCA gene mutation with ovarian cancer. Olaparib tablets are easier to use than the capsules; the capsule form required taking 2 doses of 8 capsules daily, whereas the tablet form is taken 2 times daily as 2 tablets.

Approval of maintenance treatment, the standard treatment for ovarian cancer , is based on two randomized, placebo-controlled, double-blind, multicenter studies in patients with recurrent ovarian cancer responding to platinum-based treatment.

In the clinical study called SOLO-2, patients with a BRCA gene mutation and recurrent ovarian, fallopian tube or primary peritoneal cancer, totaling 295 patients, were given 300 mg olaparib tablets twice daily or placebo (a drug containing no active ingredient). The median duration for which treatment kept the cancer under control was 19.1 months in patients given olaparib, compared with 5.5 months in the placebo arm.

In the other study, regardless of BRCA mutation status, 265 patients were divided into two arms to receive 400 mg olaparib capsules twice daily or placebo. The olaparib arm showed a statistically significant improvement: the median duration for which treatment kept cancer under control was 8.4 months, compared with a reported 4.8 months in the placebo arm.

The most common side effects (≥%20) in clinical studies were anemia, nausea, fatigue, vomiting, throat infection, diarrhea, joint and muscle pain, tinnitus, headache, indigestion, decreased appetite, constipation and mouth sores. The most common laboratory abnormalities (≥%25) were decreased hemoglobin, decreased lymphocytes, decreased leukocytes, decreased absolute neutrophil count, increased serum creatinine and decreased platelets.

The recommended olaparib tablet dose for both maintenance treatment and later-line treatments is 300 mg orally twice daily (with or without food) (two 150 mg tablets).

What is olaparib's mechanism of action?

The BRCA and PARP genes affected by olaparib take part in repairing DNA damage. If only one of these genes is defective, the cancer cell survives. However, if both are impaired, the cancer cell cannot repair DNA effectively. Researchers have succeeded in destroying cancer cells by targeting the PARP gene in patients with a defective BRCA gene. In conclusion, olaparibis a drug that targets tumor cells sensitive to DNA repair defects by inhibiting PARB, an enzyme involved in DNA repair.