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Rare cancers often present with no symptoms, meaning most women are diagnosed at an advanced stage, significantly limiting their treatment options
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EPOCH Trial to Explore Ovarian, Uterine Carcinosarcoma Therapies

International clinical trial exploring treatment combinations for rare and aggressive cancers in women launched in Australia

Walter and Eliza Hall Institute
Published:Sep 22, 2023
|3 min read
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An international clinical trial exploring a new way to treat rare and aggressive gynecological cancers has launched in Melbourne, Australia. Based on a Walter and Eliza Hall Institute of Medical Research (WEHI)-led discovery, the trial hopes to enhance treatment options for women with two of the most lethal gynecological cancers—ovarian and uterine carcinosarcoma.

The study will offer a novel combination therapy for women with these relapsing cancers and is now open in Australia, with plans to expand to Canada and the United Kingdom in the coming months.

EPOCH trial and rare cancers

In 2022, more than 1800 Australian women were diagnosed with ovarian cancer, including ovarian carcinosarcoma. Survival rates for ovarian cancer have not improved in over three decades, with one Australian woman dying from the disease every eight hours. 

Uterine cancer was the fifth most diagnosed cancer in Australian females in 2022. Uterine carcinosarcoma, while three times more common than ovarian carcinosarcoma, is still classified as a rare cancer. These diseases often present with no symptoms, meaning most women are diagnosed at an advanced stage, significantly limiting their treatment options.

The EPOCH (Eribulin and Pembrolizumab in Tubo-Ovarian and Uterine Carcinosarcoma) trial aims to reverse these dire outcomes by testing a new combination therapy. The study is funded by ANZGOG (Australia New Zealand Gynaecological Oncology Group) and developed via the International Gynecologic Cancer InterGroup. Clare Scott AM, MBBS, PhD, principal investigator of the EPOCH trial and chair of ANZGOG, said the trial could provide real hope for women with rare cancers.

“When a disease is rare, it means the research into it is much more challenging, halting the discovery of new treatments,” said Scott, who is also a joint division head at WEHI’s Clinical Translation Division. “Ovarian carcinosarcoma is currently treated with the same drugs used for the more common ovarian cancers, but these tumors generally respond poorly to standard-of-care treatments. This is proof that blanket approaches aren’t viable when it comes to rare cancers and that new treatments are desperately needed. That is why it is incredibly exciting to see our research, spanning over seven years, now translated into a clinical trial that could potentially help women living with rare diseases, like ovarian and uterine carcinosarcomas.”

Repurposed potential 

EPOCH will give women with relapsing carcinosarcoma access to two treatments that have never been used for these cancers before. The trial is based on findings from a WEHI study published in Cancer Research, which showed a chemotherapy drug used to treat advanced stages of breast cancer was more effective for ovarian carcinosarcoma than the most proven chemotherapy, platinum chemotherapy. 

Using a variety of human ovarian carcinosarcoma pre-clinical models, the team investigated whether the chemotherapy drug, eribulin, could be used to reverse a process associated with tumor progression and drug resistance, known as epithelial-to-mesenchymal transition (EMT). Holly Barker, PhD, who spearheaded the research, found the chemotherapy drug could reverse EMT in ovarian carcinosarcoma, reducing the growth and aggressive nature of these tumors. “We found eribulin specifically inhibited EMT, reducing cell invasion— which could minimize the likelihood of the tumor spreading,” said Barker. 

The team also found the drug boosted the immune response towards ovarian carcinosarcoma, as more immune cells were found in the tumors following treatment. This suggests eribulin treatment could make these tumors more responsive to immunotherapy. Early studies in uterine carcinosarcoma pre-clinical models, developed by the team, indicate Eribulin treatment is also more effective than platinum chemotherapy at reducing tumor growth for this type of cancer.              

The EPOCH trial will test this dual effect by combining eribulin with the immunotherapy drug, pembrolizumab, for the first time. “We hope the promising results we saw in our initial research will be emulated in the trial to improve outcomes for these women,” said Barker.

- This press release was originally published on The Walter and Eliza Hall Institute of Medical Research website