Perspective from the American Association for Cancer Research
In an era of significant progress against certain cancers, ovarian cancer remains difficult to detect and treat, cementing its role as the deadliest of women's reproductive cancers.
Ovarian cancer is fairly rare-about 1.3 percent of women will be diagnosed with the disease during their lifetime. However, because the disease typically goes undetected until it has reached an advanced stage, only about 46 percent of women diagnosed with ovarian cancer reach the five-year survival milestone.
Franco Muggia, MD, Professor of Medicine at NYU Langone Medical Center, senior medical oncologist at the NYU Perlmutter Cancer Center, and longtime member of AACR, has been practicing medicine for more than 50 years, with a focus on ovarian cancer. He says he has seen tremendous change and progress in the field, yet remains frustrated by the particular challenges posed by this insidious form of cancer: "The ongoing problem is that it presents too late. We're not dealing with an early disease."
Ovarian cancer often produces only mild symptoms, many of which can be explained by multiple other causes. "It's been the big problem all along," Muggia said. "When you've developed fluid in the abdomen, that is the tip of the iceberg and there has most likely already been a spread through the peritoneal cavity."
Effective, Early Screening
To date, there hasn't been an effective screening method for the disease, but 2015 brought some hope. At AACR's "Advances in Ovarian Cancer Research: Exploiting Vulnerabilities" meeting in October, keynote speaker Usha Menon, MD, discussed her ongoing work with the United Kingdom Collaborative Trial of Ovarian Cancer Screening. The large trial, spanning 14 years, showed that a screening method that tracks the protein CA-125 over time could detect twice as many cases of ovarian cancer as current methods.
The latest data from the study, published Dec. 17 online ahead of print in Lancet Oncology (doi.org/10.1016/S0140-6736(15)01224-6), indicated that screening could potentially reduce deaths from the disease by about 20 percent, although the researchers cautioned that further study is needed before any firm conclusions can be reached about the efficacy and cost-effectiveness of ovarian cancer screening.
Drug Development
The past year also brought some additions to the roster of drugs that can be used to fight ovarian cancer. In December 2014, the FDA approved olaparib (Lynparza), a PARP inhibitor, for use in treating women with advanced ovarian cancer associated with BRCA gene mutations. Also approved at the same time was the companion diagnostic test, BRACAnalysis CDx, designed to determine whether a patient has the BRCA gene mutation and thus help predict the best treatment approach.
Lynparza alone has proven effective in shrinking or stabilizing ovarian cancer tumors, and has been proven to benefit patients both with and without BRCA mutations. The drug has also been tested in combination with PI3K inhibitors and with an AKT inhibitor.
These potential combinations of drugs could help attack ovarian cancer's tendency to recur. To date, surgery followed by platinum-based chemotherapy has been the standard of care for most patients, particularly those with high-grade serous ovarian cancer, which accounts for the majority of cases. However, as many as 80 percent of women ultimately develop resistance to chemotherapy and their cancer recurs.
"One wishes we had made more progress in fighting the recurrences," Muggia said. "That's one area where the targeted therapies should play an increasing role."
Research into targeted therapies has focused on identifying women whose cancers are most likely to respond to a specific therapy, as well as identifying the optimal stage of disease at which to administer the therapy. "This is a fruitful area of investigation," he said.
Immunotherapy, which is reshaping the way doctors treat many cancers, is being examined for use in ovarian cancer patients via numerous clinical trials.
A Better Way
Muggia said that going forward he believes ovarian cancer patients would benefit from a wider use of intraperitoneal (IP) treatment, which involves the injection of chemotherapy directly into the abdomen, usually after a surgeon has debulked the tumor, in conjunction with standard intravenous methods.
Still, the method remains underused, with a recent study from six National Comprehensive Cancer network institutions indicating that fewer than half of all patients who could benefit from IP treatment receive it (JCO 2015; 33:2841-2847; OT 11/25/15 issue). The study's lead author, Alexi Wright, MD, MPH, of the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, said that use of IP treatment may be significantly affected by physicians' feelings about the procedure.
Muggia expressed the same concern: "If the data on IP therapy were 100 percent persuasive, it would be done much more frequently," he said. However, punishing side effects have been reported, especially from the high dose of cisplatin that was given in the early years of IP therapy. Studies are underway to gauge the effectiveness and tolerability of lower dosages, he noted.
Risk-reducing Surgery
The genetic qualities of ovarian cancer have prompted some women to head it off entirely by undergoing risk-reducing surgery. Actress Angelina Jolie Pitt drew widespread attention for her decision to undergo prophylactic surgery (salpingo-oophorectomy). Muggia said this surgery is a viable option for women who have finished bearing children and who have tested positive for BRCA gene mutations.
The surgery does come with its own risks and side effects, however, such as early menopause. "That introduces the dilemma of whether to take estrogen, which can potentially raise the risk of breast cancer," he said. "It becomes a personal decision, with many factors to weigh."