Clinical trial shows drug combination may be effective in recurrent ovarian cancer

June 2, 2014, Dana-Farber Cancer Institute

Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology (ASCO) meeting in Chicago today. This is the first ovarian cancer study to use a combination of drugs that could be taken orally. The drugs were tested in a phase I combination study followed by a randomized phase 2 trial sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. The trial compared the activity of the combination of the drug olaparib, which blocks DNA repair, and the blood vessel inhibitor drug cediranib, vs. olaparib alone. Trial results showed a near doubling of progression-free survival benefit for the combination therapy over use of the single drug alone.

"The findings of this study are exciting because they support the idea that combining these two targeted oral therapies results in significant activity in , more so than olaparib alone," said Joyce Liu, M.D., MPH, the lead investigator and medical oncologist at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, Boston. "We are looking forward to further exploring this combination in ovarian cancer and potentially increasing effective treatment options for our patients with this cancer."

There are over 22,000 cases of ovarian cancer diagnosed annually in the United States alone. Seventy-five percent of these cases are classified as high grade serous type, and they show more advanced disease at diagnosis and are more aggressive. Of this high-grade type, about three-quarters will regress after initial treatment but nearly all will recur and need follow-up treatment. That treatment will be based on how the cancers have responded to previous therapies and are broken down into two categories:

  • Platinum-Sensitive – these are patients most likely to benefit from PARP inhibition. PARP (Poly ADP-Ribose Polymerase) inhibitors, such as olaparib, are targeted drugs that block an enzyme involved in many functions in the cell, including the repair of DNA damage.
  • Platinum-Resistant – these are patients whose disease recurred within six months of conventional chemotherapy (using the drugs cisplatin or carboplatin) and are generally less responsive to subsequent treatments and have not responded as well to PARP inhibitors. They are currently treated with non-platinum chemotherapy, single-agents, with or without addition of the blood vessel inhibitor drug called bevacizumab.
Dr. Joyce Liu talks about her clinical trial showing drug combination may be effective in recurrent ovarian cancer. Credit: Dana-Farber Cancer Institute

An anti-angiogenic agent, or blood vessel inhibitor, called cediranib (which inhibits a protein known as VEGFR) and olaparib, a PARP inhibitor, are each clinically active in recurrent ovarian cancer. Pre-clinical studies suggest these agents add to and enhance the activity of each other, and a phase 1 study showed that the combination of cediranib and olaparib was well-tolerated with minimal side-effects. Hence, a total of 90 patients from nine centers were randomly assigned to one of two study arms for the phase II clinical trial: the first taking capsules of olaparib (400 mg twice daily) and the other taking a combination of the two drugs (200 mg olaparib in capsule-form twice daily and 30 mg tablets of cediranib once daily). The study arms were stratified by BRCA gene mutation status and receipt of prior anti-angiogenic therapy.

Patients, whose median age was 58, were enrolled from October 2011 to June 2013. As of March 2014, median progression-free survival was 9.2 months for olaparib and 16.7 months for the combination therapy, which is a significant advantage. The overall rate of toxicity was higher for patients on the . Fatigue, diarrhea, and hypertension were the most common toxic effects, all of which were manageable.

"Of particular note is the fact that both drugs used in this trial are in pill form," said Percy Ivy, M.D., associate chief of NCI's Investigational Drug Branch. "Therefore, this therapy could be used anywhere in the world where patients can be monitored for dehydration due to diarrhea side-effects and blood pressure due to hypertension side-effects."

Based on these results, two phase 3 trials are being planned for platinum-sensitive and platinum-resistant ovarian cancer patients by one of NCI's new National Cancer Trial Network Groups, the NRG Oncology Group (formerly 3 cooperative groups: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG).

Explore further: Targeted therapies offer hope against aggressive cancer

More information: Liu, JF, et al. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the anti-angiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. NCT 01116648. www.cancer.gov/clinicaltrials/ … n=HealthProfessional

Related Stories

Targeted therapies offer hope against aggressive cancer

May 31, 2014
Several new targeted therapies have shown promise against advanced cancers of the blood, lungs, ovaries, and thyroid, according to research released Saturday at a major US cancer conference.

Olaparib shows promise in treating ovarian cancer, even without BRCA mutations

August 21, 2011
The PARP inhibitor, olaparib, that has shown promise in women with an inherited mutation in their BRCA1 or BRCA2 gene (accounting for about 5-10% of breast and ovarian cancer cases), has, for the first time, been shown to ...

Targeted treatment plus chemotherapy could benefit women with ovarian cancer

October 11, 2013
Conventional chemotherapy could further extend life in some women with ovarian cancer when used in tandem with a new type of targeted treatment, a new international study shows.

Biological therapy with cediranib improves survival in women with recurrent ovarian cancer

September 30, 2013
Women with ovarian cancer that has recurred after chemotherapy have survived for longer after treatment with a biological therapy called cediranib, according to new results to be presented today (Monday) at the 2013 European ...

New drugs may make a dent in lung, ovarian cancer

May 31, 2014
New drugs are making a dent against some hard-to-treat cancers, but some results raise fresh questions about whether the benefit is worth the cost.

New drug extends life in women with advanced ovarian cancer

November 5, 2013
Women with ovarian cancer that has returned after previous treatment had their life extended by almost three months after treatment with a drug called Cediranib, according to trial results presented today at the National ...

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.