For the majority of the around 800 women diagnosed with endometrial cancer each year in Denmark, the cancer is detected early enough to make a full recovery with surgery alone. However, if the cancer has spread, additional treatment has been the same combination of two types of chemotherapy for decades. While other types of cancer have seen that the development of new, targeted treatment has improved survival rates considerably in recent years, first-line treatment for advanced endometrial cancer remains the same as it was at the turn of the millennium.
However, the results of a large, international randomized controlled trial indicate that there are major benefits from adding a new type of immunotherapy to the chemotherapy. Half of the 500 patients in the study received immunotherapy called dostarlimab at the same time as chemotherapy and for a period after. The other half received a placebo as well as chemotherapy. Twice as many of the group of patients who received dostarlimab experienced no deterioration in the cancer after two years than patients in the placebo group. Furthermore, the survival rate for the dostarlimab group was almost 25% higher.
“This is unprecedented! It’s a huge improvement: both in survival rates and the length of time with no deterioration. It means that the patients who received immunotherapy have a much better chance of living longer, at the very least. And I think some of them will make a full recovery. This is unheard of for patients with advanced endometrial cancer,” says Mansoor Raza Mirza, consultant.
As head of the international study, he has just presented the results at an online conference for cancer physicians throughout the world, and the study is published in the prestigious scientific journal New England Journal of Medicine.
Patients with particularly sensitive tumours benefit even more from immunotherapy
Mansoor Raza Mirza describes the difference between the placebo and dostarlimab groups as unprecedentedly large. However, even larger differences emerge after looking at the results more closely. One quarter of patients have what the researchers call a “hot tumour”, which means that the cancer is very sensitive to immunotherapy. Among these patients, four-times as many experienced no deterioration after 24 months. This group have a particularly large number of mutations in the cancer cells, because the repair function in their immune system is defective. This is called defective mismatch repair or dMMR.
Probability of no deterioration in the cancer after 24 months:
|Hot tumour (dMMR)||61.4 percent||15.7 percent |
|Whole patient group||36.1 percent||18.1 percent|
Probability of survival after 24 months:
|Hot tumour (dMMR) ||83 percent||58 percent|
|Whole patient group||71.3 percent||56 percent|
“Dostarlimab works by releasing the brake on the ability of the immune system to repair gene mutations in cancer cells. So it makes sense that there is a particularly high effect for patients with dMMR,” says Mansoor Raza Mirza.
Tested for other types of cancer in other studies
dMMR is not just found for endometrial cancer. The defect is also in a certain percentage of patients across all types of cancer. Therefore, dostarlimab and other immunotherapy treatments have already been approved for treating several other types of cancer where they have also demonstrated a great effect.
“The new developments are because it is not only about patients with endometrial cancer. This type of immunotherapy is being tested in other studies on patients with dMMR tumours across all types of cancer. It is part of a wave of development in new cancer treatments that can now benefit patients with endometrial cancer as well,” says Mansoor Raza Mirza.
Slightly more side effects, but better quality of life
The study observed slightly more side effects in the dostarlimab group than in the placebo group. However, for by far the majority these side effects were mild, such as diarrhoea and a rash, and they may be because dostarlimab stimulates the patient's own immune system. Patients’ assessment of their quality of life was also measured. And here too assessments were better among patients who received dostarlimab.
Neither the practitioners nor patients know which of the 500 trial subjects received dostarlimab and which received a placebo. This is normal in randomized trials in which one of the objectives is to examine whether a new medicine improves survival rates.
“These results will also affect the treatment of patients in the trial. If a patient goes into relapse, it is possible to block the trial. If she was receiving a placebo, she can be given the immunotherapy. This will affect the survival rates in the trial. But it would be unethical not to give immunotherapy to the patients who were receiving a placebo after seeing such large differences,” say Mansoor Raza Mirza.
Before dostarlimab can become part of standard treatment for advanced endometrial cancer, the product must be approved by the European Medicines Agency. After this, the Danish Medicines Council will assess the product.