According to a recent article, Krishnansu S. Tewari, MD, discussed using bevacizumab, niraparib, and olaparib in patients who have received and completed chemotherapy for their advanced ovarian cancer.

Ovarian Cancer

Ovarian cancer is a type of cancer that forms in an ovary, one of two almond-shaped organs found on each side of the uterus that store eggs and produces the hormones estrogen and progesterone. Depending on the type and stage, malignant cells are found inside, near, or on the outer layer of the ovaries. Common areas where the cancer may spread from the ovary include the abdomen lining, bowel and bladder lining, lymph nodes, lungs, and liver. There are four types of ovarian cancers:

1. Epithelial tumors, which refer to the thin layer of tissue that covers the ovaries and account for 90% of ovarian cancer cases
2. Germ cell carcinoma tumors, in which the cancer begins in the cells that form the eggs and account for 5% of ovarian cancer diagnoses
3. Stromal carcinoma tumors, in which the cancer develops in the connective tissue cells that hold the ovary together and produce estrogen and progesterone and account for 5% of ovarian cancer diagnoses
4. Small cell carcinoma of the ovary (SCCO), which is a rare, highly malignant tumor that accounts for 0.1% of ovarian cancer diagnoses

The staging of ovarian cancers is the following:

• Stage I: Cancer is found in one or both ovaries
• Stage II: Cancer has spread to the pelvis
• Stage III: Cancer has spread to the abdomen
• Stage IV: Cancer has spread to other parts of the body

Symptoms:

The frequency and/or number of symptoms are key factors in the diagnosis of ovarian cancer, and symptoms become more noticeable as the cancer progresses. Common symptoms include:

• Bloating
• Pelvic pain
• Abdominal swelling
• Loss of appetite
• Urinary symptoms (urgency or frequency)

Symptoms of a cancer within the stromal carcinoma group include:

• Abnormal uterine bleeding
• Endometrial hyperplasia (thickening of the uterus that causes bleeding)
• Breast tenderness
• Vaginal secretions
• Virilizing symptoms due to increased testosterone
• Increased abdominal girth
• Enlarging abdominal mass
• Irregularities in the menstrual cycle 

Examining Relevant Trials

The trials that Tewari talked about were SOLO-1, PRIMA, PAOLA-1, and GOG-0218. In the GOG-0218 trial, bevacizumab was introduced as a possible treatment option for ovarian cancer. In 2018, bevacizumab was approved as a frontline therapy with chemotherapy despite the finding from its studies being published back in 2011.

The PAOLA-1 study was one that looked into using bevacizumab with or without olaparib. In this particular study, bevacizumab was used as a control arm. Both SOLO-1 and PRIMA studied olaparib and niraparib which are PARP inhibitors.

Each of the studies were especially important because they were all successful in meeting their primary end points. Their primary endpoints were progression-free survival (PFS). This means that in all of the studies the occurrence of progression and death was considerably delayed.

Importance of the Trials

The trials resulted in researchers discovering that olaparib was best used for germline somatic BRCA mutations, niraparib was effective for everyone, and bevacizumab in addition to olaparib worked best in patients who are HRD positive.

It is important to note that none of these studies have any survival data yet; however, the PFS gives good indications for patients to enjoy a survival benefit.

National Comprehensive Cancer Network (NCCN)

The NCCN recommend in their guidelines that ovarian cancers in stages II, lll, and lV be treated with platinum-based chemotherapy as well as maintenance therapy afterwards. For patients who are advanced and have been given bevacizumab alongside their chemotherapy and are either germline, somatic, or BRCA mutated, they can be given niraparib, olaparib, or bevacizumab plus olaparib. In cases where the patient is stable, they should then be treated as if they had recurrent disease. If they have been given bevacizumab as their main therapy, their HRD status should be checked, and if they come back HRD positive the recommendation is for them to be treated with bevacizumab plus olaparib.

Germline and Somatic Testing

Tewari stresses that every single person who has been diagnosed with ovarian cancer should be genetically tested for BRCA1/2 and other genes that are susceptible. This testing is extremely important because it plays a role in how the patient will be treated along with other aspects.