OncoQuest's Ovarian Cancer Pipeline1,2,3,4

Ovarian cancer is the seventh most common cancer worldwide for females, with nearly 239,000 new cases diagnosed in 2012. 3 In 2015, over 1.2 million women had ovarian cancer and the disease resulted in 161,100 deaths worldwide.

The 5-year survival rate for ovarian cancer is approximately 40%. As the symptoms of ovarian cancer are non-specific and can be attributed to other conditions, e.g. irritable bowel syndrome, approximately 60% of patients are currently diagnosed once the cancer is already at an advanced (Stage III/IV). 

The risk of developing ovarian cancer is influenced by several factors, including age, lifestyle, reproductive history and family history. Women who have ovulated more in their lifetime are also more at risk from ovarian cancer. This includes women that have never had children, those who began ovulation at a younger age, or those who reach menopause at an older age. Other risk factors to developing ovarian cancer include hormone therapy post menopause, obesity, and fertility medication. Decreased risk is associated with hormonal birth control, breast-feeding, and tubal ligation.

The risk of developing ovarian cancer is also highly increased in women with specific inherited genetic abnormalities, such as mutations in the BRCA1 or BRCA2 genes, or other alterations in the genetic profile which increase the risk of developing ovarian cancer but also increase the sensitivity to chemotherapy with platinum compounds and other new agents targeting those alterations. In the general population, 1.4 % of women will be diagnosed with ovarian cancer, while mutations in these genes account for 20% of ovarian cancer cases. Women with BRCA1 gene mutations typically develop ovarian cancer younger than women with a BRCA2 gene mutation. Women with a BRCA1 gene mutation are often diagnosed between the ages of 35-50, whereas women with a BRCA2 gene mutation are diagnosed after the age of 60. Overall, the average age of diagnosis of ovarian cancer in women with a BRCA1 or BRCA2 gene mutation is 48, compared to 63 in the general population.Although complete responses are common following initial treatment with platinum and taxane regimens, within 2 years of cytoreductive surgery for Stage III/IV disease, half of tumors recur. Once the patient relapses, there is no curative therapy. Recurrent ovarian cancer is invariably fatal. Thus, there is a need for new therapies that will reduce the rates of recurrence and prolong the relapse-free intervals.

Women with BRCA1 gene mutations typically develop ovarian cancer younger than women with a BRCA2 gene mutation. Women with a BRCA1 gene mutation are often diagnosed between the ages of 35-50, whereas women with a BRCA2 gene mutation are diagnosed after the age of 60. Overall, the average age of diagnosis of ovarian cancer in women with a BRCA1 or BRCA2 gene mutation is 48, compared to 63 in the general population.7

The most common form of ovarian cancer is ovarian carcinoma, which accounts for more than 95% of all cases. There are several subtypes of ovarian carcinoma, but the most aggressive form is high-grade serous carcinoma (HGSC). HGSC is a type of tumor that forms from the serous epithelial layer in the abdominopelvic cavity and is found primarily in the ovary. HGSC cases have the lowest survival rates of all ovarian cancer patients. HGSC is the most common form of ovarian cancer, comprising approximately 70% of all ovarian cancer, As many as 90% of stage III/IV are high grade serous carcinoma. Less common types of ovarian cancer cases are germ cell tumors and sex cord stromal tumors.

There is a significant unmet need for new treatment options for ovarian cancer since the tumor tends to re-grow after an initial response to treatment in 70% of cases diagnosed at stages III/IV. Surgery and chemotherapy are the principal treatment options. In general, cancers of the ovary, fallopian tube and peritoneum are managed in the same way. Guidelines for the most appropriate initial surgical and chemotherapy management have been defined, based on the results achieved over the years in large clinical studies.

New classes of treatments such as anti-angiogenics, PARP inhibitors, and checkpoint inhibitors are all being investigated, particularly in high-grade serous carcinoma.

Treatment Options

Treatments for ovarian cancer are divided into frontline and recurrent treatments. Frontline refers to the first attempt of treatment for a patient with ovarian cancer. Recurrent treatment occurs after a patient has relapsed.

Front-line treatments typically include a combination of surgery, chemotherapy and radiation therapies. However, front-line chemotherapy often is unable to produce remission in 70% of patients with ovarian cancer and approximately 40% of women who do go into remission after chemotherapy will relapse within 3 years. Patients that are unresponsive to front-line treatments are divided into three categories: those with persistent ovarian cancer, recurrent ovarian cancer, or refractory ovarian cancer. Chemotherapy is able to prolong survival but rarely provides a cure.

Footnotes
  1. http://onlinelibrary.wiley.com/doi/10.1111/ajco.12449/full
  2. https://www.preventovariancancer.ca/what-are-the-brca1-brca2-genes
  3. Ferly J, Shin HR, Bray F, Forman D, Mathey C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr.
  4. European Network of Gynaecological Cancer Advocacy Groups, What is Ovarian Cancer?, 2017.