Report from ASCO 2011
At this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, numerous posters and presentations explored issues related to ovarian cancer. Read on for highlights of research on treatment, screening and genetics.
We hosted the webinar below summarizing research from the ASCO meeting. Dr. Deborah Armstrong of The Johns Hopkins School of Medicine was the featured speaker.
Five studies examined drugs that affect angiogenesis, a process of new blood vessel formation that is critical to tumor growth.
Researchers presented results of a Phase III trial of carboplatin and gemcitabine (Gemzar) with or without bevacizumab (Avastin) in women with platinum sensitive recurrent ovarian cancer. The OCEANS trial, as it is known, measures progression free survival (PFS), and showed a four-month improvement in PFS for women using bevacizumab. An independent review committee found an improvement in PFS of 3.7 months for the same group of women. Analysis of overall survival (OS) data is not final for the study, but interim data show a 5.6 month improvement in OS for women using bevacizumab.
Another Phase III study of bevacizumab evaluated the use of the drug as a frontline option, meaning that it is part of a woman’s first treatment for ovarian cancer. The trial used carboplatin and paclitaxel with or without bevacizumab. Updated data from the trial were presented at ASCO, and showed an improvement in PFS of 2.4 months for women taking bevacizumab. The data were analyzed separately for women diagnosed in Stage III and sub-optimally de-bulked, and for women diagnosed in Stage IV. More time is needed before this study can yield meaningful data about overall survival.
Japanese researchers presented an early phase study of 40 women receiving bevacizumab and pegylated liposomal doxorubicin (PLD). In this study, 33 percent of women responded to the treatment. The researchers report that bevacizumab appears to enhance the effect of PLD and suggest further studies of the weekly administration of both drugs.
An independent review committee received radiologic results from the GOG-218 trial, results of which were presented at last year’s Annual Meeting. That study showed an improvement in PFS in women who used bevacizumab in combination with chemotherapy and as maintenance therapy. The committee reviewed the data to confirm results of this trial, and agreed with the results in approximately 75 percent of images reviewed, validating the study. This confirms that the treatment arm, bevacizumab and chemotherapy plus bevacizumab maintenance, did show an improvement in PFS.
A phase II study of docetaxel plus aflibercept, a VEGF (cell growth factor) inhibitor, in recurrent ovarian cancer showed that approximately 50 percent of patients had tumors that responded to the treatment.
Results from the CALYPSO trial were presented at the ASCO meeting.
Researchers presented results of a Phase III trial comparing carboplatin and pegylated liposomal doxorubicin (PLD) to carboplatin and paclitaxel in very platinum sensitive ovarian cancer patients. “Very platinum sensitive” was defined as a greater than 24-month platinum free interval. The PFS times for each arm were similar (12 months in the C-PLD arm versus 12.3 months in the C-P arm). More harmful side effects were seen in the C-P arm although there was no difference in overall survival.
Trabectedin, also known as Yondelis, continues to be explored in ovarian cancer.
A Phase II trial of trabectedin in recurrent ovarian cancer measured patient response to the drug. Of the 44 women in the trial, slightly more than half were platinum sensitive. More than half of the women in the trial had three previous treatments. About half of all patients had either a partial response or stable disease when treated with trabectedin, but the response rate was higher for platinum sensitive patients.
However, final results of OVA-30—a Phase III trial comparing trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD alone—did not show a significant increase in overall survival for those treated with trabectedin. Almost 700 women were enrolled in this trial, which showed a slight improvement in PFS for women in the trabectedin arm. The researchers analyzed women based on their progression free interval and found that women who had a recurrence six to 12 months out of treatment responded better than other women in the study. Future trials may target women who have a recurrence in this interval.
PARP Inhibitors, drugs that affect the Poly ADP ribose polymerase (PARP) enzyme—a protein that helps repair damaged DNA, were also the focus of several studies presented at the ASCO meeting.
An in vitro study by the National Cancer Institute explored the effects of PARP inhibitors on DNA. The study, which examined the timing of using the PARP inhibitors olaparib and carboplatin found that exposing cancer cells to PARP inhibitors before chemotherapy may decrease the effect of chemotherapy. A trial is currently open that explores the sequencing of PARP inhibitors and platinum based chemotherapy in women.
A Phase I study of the PARP inhibitor olaparib in combination with the anti-angiogenic cediranib in recurrent ovarian cancer showed a fairly high response rate, but also some serious toxicities.
A Phase II study of the PARP inhibitor olaparib in patients with platinum sensitive recurrent ovarian cancer showed an improvement in PFS (8.4 months for the treatment arm versus 4.8 months for the placebo arm) and increased adverse events such as abdominal pain, fatigue, anemia and nausea for the women on olaparib.
Several studies explored new drug compounds for women with ovarian cancer.
Last year’s ASCO meeting included a data on a new compound called NKTR-102. Further studies on NKTR-102 showed high levels of overall response rate—meaning some observable effect—when tested on 71 women with platinum resistant or refractory ovarian cancer. The median PFS for women in this trial was 5.5 months and median OS was 14 months. Some severe side effects were noted, specifically high grade diarrhea, nausea and vomiting. Neuropathy and alopecia were not observed.
Results of a Phase II trial of a compound called EC145 plus pegylated liposomal doxorubicin (PLD) versus PLD alone in women with platinum resistant ovarian cancer showed an improvement in PFS. Women who were folate receptor positive (80 percent of the women in this study) had greater than average improvement.
A Phase II study was presented in which catumoxomab, an antibody, was given intraperitoneally during and after surgery, before beginning standard chemotherapy. The study measured disease free and overall survival. The study found that giving the antibody is feasible although long term survival still needs to be evaluated.
A Phase I safety study of farletuzumab, carboplatin and PLD in 15 women with platinum sensitive ovarian cancer found the combination of drugs to be fairly well tolerated, with no severe adverse events yet reported.
Results of a large screening trial were presented. More than 78,000 women were randomized between normal care and screening arms. The screening protocol involved annual CA-125 testing for six years and a transvaginal ultrasound for four years. The study was designed to show the effect of screening on overall survival by following patients for 13 years. The study showed that more women were diagnosed in the screening arm, but more women died of ovarian cancer in the screening arm. Additionally, more than 3,000 women had surgery based on false positive results, leading to more than 160 women with serious complications. This study showed that screening with this protocol did not reduce ovarian cancer mortality.
An Australian study suggested that all women with ovarian cancer be tested for BRCA mutations. The study found that 13 percent of women diagnosed with ovarian cancer had a BRCA mutation, and more than 50 percent of them did not have a family history of breast or ovarian cancer. In addition, the study found that women with a BRCA mutation have tumors that respond better to platinum treatment and may be eligible for treatment options such as PARP inhibitors.
A study of 21 women with BRCA mutations showed that paclitaxel may be an active drug in BRCA mutated ovarian cancer (BMOC), and that platinum resistant BMOC patients were more sensitive to using paclitaxel as a single agent.