News
New drug combination offers hope to ovarian cancer patients
Nearly half of the women treated with avutometinib and defactinib saw their tumours shrink significantly, results show
Thousands of women with ovarian cancer could benefit from a drug combination thought to be nearly twice as effective as the next best treatment.
Scientists hope the results, presented at the world’s largest cancer conference, will lead to a new option for patients with advanced low-grade serous ovarian cancer (LGSOC), a rare form of the disease that has a poor response rate to current treatments.
The international study, led by researchers from The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, has tested avutometinib alone and in combination with defactinib in 29 patients with LGSOC.
Both drugs are designed to block signals that encourage cancer cells to grow.
Approved treatment options available for patients with advanced LGSOC in the UK are currently limited to chemotherapy and hormone therapy, with response rates typically ranging from 0-14 per cent.
According to these results, nearly half (45 per cent) of patients treated with avutometinib in combination with defactinib saw their tumours shrink significantly, suggesting the new combination could be almost twice as effective as the next best treatment.
Responses to the drug combination were particularly promising in those with a mutation in a gene called KRAS, with six in 10 patients experiencing significant tumour shrinkage.
LGSOC accounts for about one in 10 cases of ovarian cancer, with around 700 women in the UK and 80,000 worldwide diagnosed each year. Compared with other forms of the disease, LGSOC tends to affect younger women.
Global lead investigator of the study, Dr Susana Banerjee, consultant medical oncologist and research lead for The Royal Marsden NHS Foundation Trust gynaecology unit, said: “These initial results could be fantastic news for women with low grade serous ovarian cancer, indicating a far more effective option than current treatments may be on the horizon.
“It’s wonderful to see so many patients experience a meaningful response to this innovative drug combination and I’m so grateful to all who joined the trial, making this research possible.
“Low grade serous ovarian cancer does not respond well to currently approved treatments, so these results could represent a significant breakthrough in treating the disease.
“We are hopeful this drug combination will one day become a standard of care for women with low grade serous ovarian cancer.”
Avutometinib is a dual RAF and MEK inhibitor, a type of targeted drug that blocks certain proteins that help control cancer growth and survival. Studies have shown the drug can become ineffective over time as tumours develop resistance to treatment.
However, when combined with defactinib – which is designed to combat a protein that encourages drug resistance – researchers believe avutometinib works more efficiently. The drug combination is over four times more effective than avutometinib alone.
Christine Cull, a 71-year-old from Coventry, was diagnosed with low grade serous ovarian cancer in 2009. She found out the disease had returned in 2014 and she was treated with chemotherapy and hormone therapy, which didn’t work for her, along with several surgeries.
She joined the trial at The Royal Marsden in August 2020 and has been treated with the new drug combination ever since. Her latest scan results showed no evidence of disease.
“My lowest point throughout this experience was in 2019 when my local hospital said there was nothing more they could do for me – it was horrible,” Cull explained.
“My cancer had completely resisted chemotherapy and hormone therapy, and my team weren’t able to operate again.
“Fortunately, my doctor referred me to The Royal Marsden who, as specialist cancer centre, had the expertise to do another surgery. When the disease started growing again the next year, this trial had opened at the hospital, and I was chuffed to be able to join.
“I have scans every three months and each time we’ve seen the cancer getting smaller and smaller. After finding out recently that the cancer is currently not even visible on scans, I felt relieved, amazed and so happy to be able to pass this good news onto family and friends.”
Cull said the hospital gave her and her family hope when she thought all her options had been exhausted.
“The Royal Marsden means so much to me. Because of this trial, I am able to live my life with my husband, three children and three grandchildren with barely any side effects.”
Small bowel microbiome differences between women and men may help explain why some conditions are more common in women, a study suggests.
The small bowel microbiome is the community of microorganisms living in this part of the digestive tract, where they play vital roles in immune function, metabolism and hormonal regulation.
Researchers found differences between women and men in the composition and organisation of these microbial communities. One bacterial community containing Granulicatella was found only in women.
The study was conducted by investigators at Cedars-Sinai Health Sciences University.
Ruchi Mathur, director of clinical research and clinical operations for the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and corresponding author of the study, said: “One intriguing finding was a bacterial community containing Granulicatella, which we found only in women.
“Bacteria in this community appear at increased levels in women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.”
The researchers also identified differences between women and men in how microbes in the small bowel produce fructans, complex carbohydrates known to trigger digestive symptoms in irritable bowel syndrome (IBS).
IBS is far more common in women than men.
Mathur, who is also a professor of medicine, said: “Our findings show that biological sex is a critical variable in the small bowel microbiome.
“We must consider it as we move toward more personalised approaches to understanding and treating disease.”
An experimental cancer drug reduced bone loss and body fat in mice modelling post-menopausal changes, early research suggests.
The compound, CADD522, appeared to strengthen bones and help the animals stay leaner after surgery designed to mimic hormonal changes seen after menopause.
The treatment remains at an early experimental stage and has so far only been tested in animals.
The study, led by the University of East Anglia, investigated CADD522, which was originally developed to block a protein involved in the growth and spread of several cancers.
Mice treated with the compound for eight weeks showed significant improvements in bone health. Scans found increased bone volume and better preservation of the honeycomb-like structures inside bones that are crucial for strength and resilience.
Blood tests suggested the treatment stimulated new bone growth without interfering with the body’s normal process of breaking down and rebuilding bone.
Dr Darrell Green, lead researcher from UEA’s Norwich Medical School, said: “Osteoporosis affects around one in three women over the age of 50, leaving sufferers vulnerable to painful fractures that can seriously impact quality of life.
“Current treatments exist, but many are plagued by side effects, safety concerns or inconvenient dosing schedules that make long-term use difficult.”
The researchers also found that mice receiving CADD522 weighed less than untreated mice despite eating the same amount of food.
They had less body fat and fewer fat deposits in their bone marrow, a process commonly seen after menopause and linked to declining bone health.
The team also examined brain tissue and found that the drug appeared to reverse several menopause-related changes in fatty acids.
Levels of omega-3 fats including DHA remained largely intact, while several other lipid abnormalities shifted back towards healthier patterns.
Green said: “We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems.”
Safety experiments in mice, rats and dogs found that CADD522 could be taken orally and was well tolerated.
The compound also appeared to be metabolised more slowly in human tissue than in rodents, potentially improving its performance in people.
“This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” added Green.
The research was led by UEA in collaboration with the University of Maryland, the Scintillon Research Institute in San Diego and the University of Stirling.
Safety testing was funded by The Sir William Coxen Trust as part of the development of CADD522 as a childhood cancer treatment.
Weight loss surgery was linked to more regular periods and fewer polyendocrine metabolic ovarian syndrome (PMOS) symptoms in women aged 18 to 45 living with obesity in a recent study.
The researchers recommend that women undergoing the procedure have access to preconception care and reproductive counselling to support their reproductive health.
Researchers at the University of Surrey analysed data over 24 months from 84 women who underwent bariatric surgery and 18 women living with obesity who did not have surgery.
Of those who underwent surgery, 49 had gastric bypass procedures and 35 had gastric sleeve surgery.
Women who underwent metabolic bariatric surgery lost more than 30kg on average at 12 and 24 months after the procedure.
Among women with polycystic ovaries, the condition persisted in only 10 per cent after 24 months.
Women also reported a resolution of clinical hirsutism, or excess body hair, by 12 months.
Women who had previously experienced irregular periods reported more regular menstrual cycles after surgery.
Professor Martin Whyte, co-author of the study and professor of metabolic medicine at the University of Surrey, said: “A large proportion of those undergoing bariatric surgery are women of reproductive age, who may be planning a pregnancy in the coming years.
“So much remains unknown about the impact of this type of surgery on women who are planning to have children.
“This raises the question of when the ideal time after surgery is to conceive.”
Women have a higher prevalence of obesity than men, with 57 per cent of women in the UK classified as overweight and 27 per cent living with obesity, which can affect fertility and the health of an unborn baby.
The researchers said 17 women had healthy pregnancies following surgery.
Although this was not specifically examined in the study, no difference in birth weight was observed between babies conceived within or after the first year.
Dr Kathryn Hart, co-author of the study and associate professor in nutrition and dietetics at the University of Surrey, said: “What we have found is that bariatric surgery positively affects the reproductive health of women living with obesity and can improve the likelihood of them having a healthy pregnancy after surgery.
“Dysregulated hormone levels, irregular periods and conditions such as polycystic ovaries are affected by obesity.
“By reducing this, what we have seen is that it can lead to improvements without the need for medication.
“We would suggest that clinicians consider medical intervention for obesity to treat irregularities in the menstrual cycle and issues with fertility.”
Diagnosis2 weeks agoMajor UK study could be a ‘game-changer’ for heavy periods and endometriosis
Entrepreneur7 days agoKOVE Medical raises €1.7 million to improve safety of foetal surgery
Fertility2 weeks agoOne week left to apply: W Accelerate with Merck KGaA and M Ventures
Mental health1 week agoUK study aims to transform maternity care for high-risk pregnancies
Menopause2 weeks agoQuarter of women miss work due to menstual symptoms, survey finds
Mental health2 weeks agoPMDD after SSRIs or hormones: Why the brain may be the missing treatment target
Diagnosis2 weeks agoArk Surgical secures further institutional backing to accelerate US expansion
Menopause5 days agoMenopause hormone treatment may ease brain fog, study suggests
1 Comment