A breakthrough in the treatment of advanced endometrial cancer. Will it help all patients?

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Endometrial cancer is one of those cancers in which there have been no breakthroughs in treatment for years. While new, effective therapies have been regularly appearing in other gynecological cancers, knowledge of the biology of this disease has remained insufficient. The situation changed a few years ago with the distinction of molecular types of endometrial cancer. And although new effective drugs have appeared in the B.148 drug program, 8 out of 10 patients with advanced or recurrent endometrial cancer still do not have access to innovative treatment.

Endometrial cancer is the third most common cancer affecting women. It is not as common as breast or lung cancer , but in the last twenty years it has seen a dramatic increase in mortality: by 5% per year. Unfortunately, this trend is consistent with the WHO forecast, according to which the number of deaths due to endometrial cancer will increase by 60% by 2040.

– The increasing incidence of endometrial cancer is associated with lifestyle risk factors, such as obesity and diabetes. 34% of all endometrial cancer cases can be attributed to excess body weight, and the presence of metabolic syndrome, including high blood sugar or hypertension, doubles the risk of developing this cancer – sums up Prof. Dagmara Klasa-Mazurkiewicz, Ph.D., MD, Department of Perinatology, Faculty of Medicine, Medical University of Gdańsk.

Endometrial cancer occurs mainly in women over the age of 50, i.e. in the perimenopausal age or after menopause. It is called vocal cancer , which means that even in the early stages its symptoms cannot be missed. According to studies, in 90% of patients with endometrial cancer, such a signal is bleeding after menopause.

In the group of women who still menstruate, spotting between periods or heavier periods may occur. It is worth remembering that abnormal bleeding does not immediately mean endometrial cancer, but each requires urgent consultation with a doctor, because it may suggest other gynecological problems.

Only twelve years ago, in 2013, molecular types of endometrial cancer were distinguished, which consequently after another eight years translated into the possibility of performing molecular diagnostics , and thus changing the patient's treatment path. The stage of endometrial cancer according to the new FIGO scale with the molecular classification of the tumor added to it has been used only since 2023.

However, the last two years have been a huge breakthrough for this group of patients. Currently, the diagnostic results divide patients with endometrial cancer into several subgroups depending on biomarkers, but for two we have registered therapies: dMMR patients characterized by a deficiency of the DNA repair mechanism (20% of the population) and non-dMMR (pMMR) with an efficient repair mechanism (80%).

The first group of patients under the B.148 drug program gained access to immunotherapy, which is extremely effective in the case of their disease. These patients may be qualified for treatment with dostarlimab (first and second line) or pembrolizumab (second line).

Unfortunately, despite progress, the majority of the population of patients with advanced or recurrent non-dMMR endometrial cancer still do not have access to innovative treatment. This means that 8 out of 10 patients cannot benefit from immunotherapy.

- In oncology, we talk about "cold" and "hot" tumors. "Hot" tumors, in the case of endometrial cancer dMMR, visible to the immune system respond well to immunotherapy. "Cold" tumors - non-dMMR - are poorly visible to the immune system. Therefore, in this case, the results of treatment with this therapy were not so spectacular. However, it is possible to increase the response by "heating the tumor". This is how the PARP inhibitor works, which introduces changes in the tumor microenvironment, making the tumor more visible. In combination with durvalumab used in non-dMMR patients, it more than doubles the duration of the response to treatment. This means twice as long a time without relapse or progression of the disease - said Dr. Anna Dańska - Bidzińska, Clinic of Gynecological Oncology, Maria Skłodowska-Curie National Institute of Oncology - State Research Institute, President of the Management Board of the Association of Women of Polish Oncology Rak Misja.

Currently, knowledge of the patient's molecular status, dMMR or non-dMMR, is crucial in planning the therapeutic path and has a significant impact on the patient's prognosis. Additionally, following the guiding principle of oncological treatment - earlier is better, it is worth implementing effective treatment already in the first line. Patients with dMMR endometrial cancer already have access to such therapy.