While hundreds of studies on ovarian cancer were presented at the 2010 ASCO Annual Meeting, many were early investigations that require further study and others confirmed results of prior studies. Some large scale studies were presented. The results of selected studies are summarized below.
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A small scale screening study was presented lending support to the development of a screening method for ovarian cancer. The study, authored by Dr. Karen Lu of M.D. Anderson Cancer Center, followed more than 3,000 women for eight years, measuring their CA-125 levels annually. These women were aged 50 – 74 and of average risk of developing ovarian cancer. Those women whose CA-125 levels were rising over a number of years were given an ultrasound, and if the ultrasound showed positive results (i.e., presence of a tumor), underwent surgery. Of the 3,328 women, 85 had an ultrasound and eight had surgery. The surgeries led to diagnosing five ovarian cancers – 3 invasive and 2 borderline – all in early stage (1-2). Two patients had benign ovarian tumors and a third had an endometrial cancer. Two women with borderline ovarian cancer were not diagnosed through these methods.
This study shows that monitoring CA-125 levels over time in women of average risk for ovarian cancer is feasible and requires no more than 3 operations for each case of cancer diagnosed. Scientists are now waiting for the results of a similar but much larger trial taking place in Great Britain which may also show a survival benefit to this manner of screening; results may be available as soon as 2012.
Recommendations: If you are of average risk of developing ovarian cancer, please consider enrolling in a screening trial. Sites for this particular trial are in Houston, TX, Dallas, TX, Providence, RI and Des Moines, IA. If you are at high risk of developing ovarian cancer, please talk to your doctor about a monitoring protocol.
The Gynecologic Oncology Group presented the results of GOG 218, a three- arm study showing an increase in progression free survival in women who used Avastin (bevacizumab) in combination with chemotherapy and as maintenance therapy. The trial showed that those women who received Avastin during chemotherapy and then received 10 months of Avastin alone had an additional median of 3.8 months before their ovarian cancer advanced. Women in this arm had a 29 percent reduction in risk of progression, and a 39% improvement in Progression Free Survival.
The side effect profile for women in the Avastin maintenance arm was encouraging – fewer than three percent of women had gastrointestinal complications, including bowel perforations. Compared to the control arm, women in the Avastin maintenance arm had an increased risk of hypertension.
We await Overall Survival data from this trial, as well as the data from future trials exploring the use of Avastin.
A Phase II trial showed promise in a new formulation of an old drug, irinotecan, as a potential treatment for women with platinum resistant or refractory ovarian cancer. Response rates were at the high end of what is expected for ovarian cancer therapies – remarkable because all of the women had resistant or refractory disease. The drug showed response in one-fifth of women whose tumors were not responsive to platinum based therapies, as well as in some women whose tumors were not responsive to pegylated liposomal doxorubicin (Doxil). Additionally, in this study, toxicity was less than one would predict from previous trials of similar drugs and. women had an average progression free survival of 18 weeks. The drug showed response in one-fifth of women whose tumors were not responsive to platinum based therapies, as well as in some women whose tumors were not responsive to pegylated liposomal doxorubicin (Doxil).
In this study, platinum refractory was defined as recurrence during platinum based therapy or one to three months after stopping therapy; platinum resistant was defined as a recurrence three to six month after stopping a platinum based therapy. Women with platinum resistant or refractory disease have fewer treatment options, meaning these results are especially welcome.
Studies presented at ASCO continued to explore the role of the BRCA mutations in ovarian cancer. One poster presented showed that for BRCA1 mutation carriers, prophylactic oophorectomy (removal of the ovaries as a preventive method) was cost effective. For BRCA2 mutation carriers, prophylactic mastectomy (removal of the breasts as a preventive method) was the most cost effective intervention.
PARP (Poly (ADP-ribose) polymerase) inhibitors continued to be explored for ovarian cancer patients with BRCA mutations and family history of breast and ovarian cancer. One Phase II trial of olaparib showed a high overall response rate greater than 40 percent, a median Progression Free Survival of 3.8 months and total Overall Survival of 7.6 months.
Other Genetic Mutations
Posters showed that women do not receive referral to specialists for genetic testing as often as necessary. The studies show that continued educational outreach to primary care providers and patients is necessary.
Women who have a family history of breast, ovarian or colorectal cancer should consider seeing a genetic counselor to discuss genetic risk and genetic testing.
Many studies presented at ASCO use intermediate endpoints, such as CA-125 levels to measure efficacy of drugs. One study, however, notes that CA-125 levels do not always correspond with imaging, and recommend that trials continue to use imaging to measure disease progression. In another study, early decrease in CA-125 levels is prognostic for longer progression free survival in women with ovarian cancer. Other studies identified new biomarkers for detection of ovarian cancer, including KLK5 which is found in the blood of women with malignant ovarian masses, and is a prognostic marker for progression free survival when measured in ascites and blood. The high mobility group A2 (HMGA2) gene is thought to be active in ovarian cancer, and may serve as a prognostic or predictive marker, or eventually a target for therapy.
Numerous studies presented at ASCO confirm that aggressive surgery leads to better outcomes for women with ovarian cancer. This surgery may involve removal of parts of the colon which did not significantly affect quality of life, as measured in one study. Another study concluded that laproscopic surgery can be used for debulking some women with ovarian cancer. However, aggressive surgery continues to be linked to better outcomes; one study showed that optimal debulking gives patients a median overall survival of 80 months.
The Ovarian Cancer National Alliance suggests that women suspected of having ovarian cancer see a gynecologic oncologist for their initial surgery.
Other New Drugs
Numerous studies explored the use of new drugs, new combinations or reformulations of existing drugs and compounds to treat ovarian cancer. These drugs ranged from new formulas of existing drugs, using existing drugs for ovarian cancer, and new classes of drugs. Drugs already approved for other diseases, including acute lymphoblastic leukemia and breast cancer were studied in ovarian cancer.
For example, the monoclonal antibody farletuzumab was studied – one Phase II trial showing safety and efficacy of the drug as a single agent in platinum refractory/resistant ovarian cancer. Another study of the drug gave patients a remission equal or longer than the first remission and high response rates.
A Phase II study of a new angiogenesis inhibitor (AMG 386) showed response rates and an acceptable safety profile suggesting the need for further studies of the agent.
Numerous studies were presented on the drug Yondelis (trabectedin). One study compared the use of Yondelis and Doxil to Doxil alone; the patients on the Yondelis arms had slightly superior response rates, progression free survival and overall survival. Another study showed promising safety data from long term use of Yondelis. Another study explored the use of Yondelis as a single agent in relapsed ovarian cancer, showing a 30 percent overall response rate and a median time to progression of 5.3 months.
In 2009, a Food and Drug Administration (FDA) advisory panel recommended that the drug undergo further studies before approval. The drug is not FDA approved for any uses.
Survival and Quality of Life
Studies exploring survival and quality of life were presented. One study showed that women with ovarian cancer who survive initial treatment will have improved outcome with each year of survival.
Patients with platinum sensitive recurrent disease have varied prognoses. Standard definition of platinum sensitivity can’t accurately predict survival outcomes. A new algorithm presented combines five characteristics that improves prognosis of PFS which may be a tool for individualizing treatment by stratifying risk groups.
One study explored the interval between neoadjuvant chemotherapy and debulking surgery in women with recurrent late stage ovarian cancer. The study showed that waiting more than six weeks after chemotherapy for surgery worsens outcomes.
Other studies explored the topic of age and ovarian cancer treatment. One such study showed that younger women with advanced ovarian cancer had more surgical procedures and cycles of therapy. Elderly women were less likely to receive standard therapy of carboplatin and paclitaxel although the side effect profiles of standard treatment or carboplatin as a single agent are similar. Age should not be a limiting factor in recommending standard treatment. Also, older women with advanced ovarian cancer are less likely to understand that their disease is incurable. This may be due to factors including the physician’s style and content of communications; however, both the patient and physician must be clear on goals of therapy.
Many Phase II trials for treatment of recurrent ovarian cancer were presented with mixed results. Some of these potential treatments, including monoclonal antibodies, topoisomerase inhibitors, angiogenesis inhibitors and other agents showed some activity in Phase II trials and warrant further study.
*This summary brought to you by the Ovarian Cancer National Alliance with thanks to the Research Advocacy Network