Addenbrooke’s oncologist welcomes NICE decision to approve GSK drug for advanced endometrial cancer
An Addenbrooke’s consultant has welcomed the decision to make an immunotherapy for advanced endometrial cancer available on the NHS in England for the first time, writes Paul Brackley.
Dr Joo Ern Ang told the Cambridge Independent that dostarlimab was the first new treatment in this indication for years.
The National Institute for Health and Care Excellence announced on Tuesday (February 8) that the drug – marketed by GSK as JEMPERLI – would be available under the Cancer Drugs Fund. It can now be used to treat a group of patients with a common and aggressive form of advanced endometrial cancer, which is cancer of the womb lining.
GSK said there are around 7,700 new cases of endometrial cancer each year in the UK and it estimates that more than 170 women of them could be eligible for the drug. Clinical trials showed it increases the chance of stabilising or slowing progression of the disease.
Dr Ang, a consultant medical oncologist in the Department of Oncology at Cambridge University Hospitals NHS Foundation Trust, said: “Typically, if endometrial cancer is diagnosed at an early stage, treatments tend to be curative and after the initial treatment, the five-year survival rate is high, in the order of 95 per cent.
“But when it is diagnosed at a late stage, the five-year survival is typically less than 20 per cent.
“For patients whose disease progresses or who relapse following first-line platinum chemotherapy, we are looking at median survival of less than 12 months.
“It’s been many years with no new drug approval for endometrial cancer. The existing standard of care has been in place for a long time.”
Patients with early-stage endometrial cancer will typically undergo surgery, while standard treatment may involve platinum-based chemotherapy or hormone options. These treatments are often given after surgery to prevent the cancer returning, or for those in whom surgery is not possible.
Once endometrial cancer reaches an advanced stage, options are limited. Only 15 per cent of women diagnosed with this late-stage disease survive for five years or longer.
“In this indication for which dostarlimab has received approval, there really is no standard of care – this is the first,” explained Dr Ang.
Dostarlimab is an immunotherapy that is administered by a 30-minute intravenous infusion.
“It is an antibody that is designed to block a receptor called programmed death receptor-1, or PD-1,” said Dr Ang. “This is a protein that is present on T cells and is a key part of our immune system.
“So this treatment augments the body’s own immune responses to attack cancer cells. In itself, it doesn’t kill cancer cells. It works by switching on the body’s immune system.”
In normal function, PD-1 works to help regulate the body’s immune system, preventing over-stimulation of the immune system in peripheral tissues. But in cancer, it helps tumours evade our natural response.
“PD-1 blinds your T cells to the presence of foreign invaders such as cancer, so by switching it you are allowing our immune defences to regain visibility of cancer cells,” explained Dr Ang, who is the gynae-oncology lead in the National Institute for Health Research (NIHR) for the Eastern region and provides oversight on clinical trials for immuno-therapy in gynaecological cancers.
The trial for GSK’s new drug – which Dr Ang was not involved in – was called GARNET and involved 108 patients.
“The response rates were high,” observed Dr Ang. “The way we define response in oncology is the reduction in the dimensions of tumour lesions in scans of more than 30 per cent.
“Here, 46 per cent of patients had disease shrinkage by more than 30 per cent and 57 per cent had either a complete response – which is the disappearance of all lesions from scans, or a partial response, which is 30 per cent shrinkage, or disease stability. The responses were very durable. At 12 months, the probability of having a maintained response was 91 per cent, which is really high.
“The toxicity profile also compares favourably with chemotherapy.”
Only 9.5 per cent of patients had severe treatment-related toxicities, while only four per cent had treatment discontinued as a result.
“The drug is designed rationally to impact the body’s immune defences. This represents a departure from how cancer drugs were researched and discovered years ago, where drug screens of natural and synthetic compounds were the norm,” noted Dr Ang.
Immunotherapies have not always delivered on their great promise. But Dr Ang believes we are getting better at using them for precision medicine.
“This is not the only PD-1 agent out there, but it’s the first to gain NICE approval in endometrial cancer. With melanoma and kidney cancers and a number of other solid tumours, we have used PD-1 agents for a number of years already
“If you look at this approval, it is for a molecularly selected group of patients. It is this group whose response is quite high and quite marked,” he said.
NICE approved the drug in adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer whose cancer has progressed on or following prior treatment with a platinum containing regimen.
dMMR / MSI-H is a genetic deficiency believed to contribute to the cancer spreading particularly quickly, making it difficult to treat with standard chemotherapy.
Uterine cancer is the fourth most common cancer in females in the UK and 94 per cent of cases occur in the endometrium, according to Cancer Research UK. Endometrial cancer is the seventh most common cause of cancer death in the UK.
Dr Ang advised any women with unexplained post-menopausal bleeding to see their GP.
Jack Harris, vice-president UK oncology, GSK said: “The availability of new treatment options for endometrial cancer have been long overdue and changing this has been a key goal of ours for some time.”
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