A Patient Benefits From Participation in a Clinical Trial of a New Treatment for Relapsed Ovarian Cancer
Not long ago, Donna and her boyfriend made a 3,000-mile road trip across the country to sightsee and visit family members. Thanks to her participation in a clinical trial under way at Memorial Hermann-Texas Medical Center, she was able to travel while continuing chemotherapy with a new drug for women who have relapsed ovarian cancer. To be eligible for the trial, patients must have responded to previous platinum-based chemotherapy and have a harmful mutation in either the BRCA1 or BRCA2 gene.
The drug is olaparib, which stops an enzyme called PARP (poly [adenosine diphosphate-ribose] polymerase) from working. “In normal cells when a strand of DNA is damaged, PARP helps to repair it,” says Joseph Lucci III, M.D., site principal investigator for the trial and a professor in the department of Obstetrics, Gynecology and Reproductive Sciences at McGovern Medical School at UTHealth. “The BRCA1 and BRCA2 genes produce tumor-suppressing proteins, providing another way to repair damaged DNA; cancer cells that do not have these proteins due to mutation in the genes are unable to repair themselves. When both ways of repairing damaged DNA are not working, cancer cells die, which makes olaparib of clinical interest for the treatment of women with advanced BRCA-mutated ovarian cancer.”
Donna is among the women to benefit from the tumor-blocking effects of olaparib, which is marketed under the name Lynparza™. Diagnosed with breast cancer in 1979 during her third pregnancy, she underwent a mastectomy at the age of 33, a week after the birth of her daughter. Both her mother and her mother’s sister were treated for breast cancer; because of her family history she decided to undergo a second mastectomy a year later. She remained cancer free until 2011, when she was diagnosed with primary peritoneal cancer, a relatively rare malignancy that develops most commonly in women and is a close relative of epithelial ovarian cancer.
Donna started chemotherapy in 2011, finishing three rounds followed by a hysterectomy. After the surgery, she underwent another five rounds that reduced her score on the Cancer Antigen 125 test (CA 125) – used to look for early signs of ovarian cancer in women at very high risk – to the normal range. She completed chemotherapy in April 2012. A year later the cancer recurred, and she underwent another six rounds of chemotherapy under the care of Dr. Lucci.
In 2015, when her cancer recurred, he offered her the opportunity to enroll in the clinical trial of olaparib. Approved in capsule form by the FDA for the treatment of women with advanced BRCA-mutated ovarian cancer, the current study is evaluating an experimental tablet form of the drug administered at a different dose. Approximately 411 patients will take part in the study in 15 countries worldwide. Donna, who is 70, was enrolled in September 2015.
“Olaparib is commercially available with limited access to women with BRCA mutations who have failed other forms of chemotherapy,” says Dr. Lucci, who is director of the division of Gynecologic Oncology at McGovern Medical School. “Through the trial, they don’t have to fail as many drugs before being able to access olaparib in tablet form. Participants come in to the office once a month, which allows us to assess their response and monitor any side effects. It’s a good choice for patients who want to maintain their lifestyles and activities.”
Participants remain in the trial as long as they continue to have a positive response – until progression or toxicity. “Donna responded quickly to the medication – her CA 125 was normal by January – and she has maintained that response,” Dr. Lucci says. “She developed a low red blood cell count, which can happen with olaparib, and had a transfusion, but in general she has tolerated the drug well with minimal side effects and much less toxicity than any of the other chemotherapy drugs she’s taken in the past. She’s a delightful person who’s very active and continues to live her life.”
Dr. Lucci points out that limited therapies are available for patients with BRCA-mutated ovarian cancer. “Olaparib is the only commercially available PARP inhibitor, but others are coming on the market,” he says. “Currently the drug is restricted to patients with germline mutations – any detectable and heritable variation in the lineage of germ cells. In the future, we expect it to become more available and in broader use, which is good news for these patients.”