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According to a recent US study, adding immunotherapy to traditional chemotherapy showed a significant reduction in disease growth in patients with advanced endometrial cancer. How to rapidly evolve support?
Immunotherapy continues to improve the management of cancers. After melanoma, lung cancer, triple negative breast cancer, a new application for a solid tumor is highlighted. The study published on March 27, 2023 in the New England Journal of Medicine, reports important results in advanced endometrial cancer. Originating in the lining of the uterus, it is one of the few cancers whose incidence and mortality rate continue to rise.
Immunotherapy: Identifying the best responders
In this randomized, double-blind, phase III trial (neither the patient nor the physician knows whether they are providing immunotherapy or placebo plus chemotherapy), 816 participants with stage 1 endometrial cancer advanced (stage III or IV) were divided into two groups according to the MMR status of their disease.
What is the MMR status of a tumor?
In the normal functioning of a cell, there is a mismatch repair system (MisMatch Repair, MMR), or “copy errors” that can occur during DNA replication. But in some cancers or in the case of Lynch syndrome, this repair system no longer works properly, which results in an accumulation of mutations in the cells.
Different terms are used or have been used to define whether or not the MMR system is functional in a tumour: MSI (microsatellite instability) or MSS (stable microsatellite) tumor, dMMR tumor or pMMR (for deficient MMR tumor and proficient MMR tumor from Anglo -Saxons). pMMR is the “normal” state our cells are in, where the MMR pathway is active and functional. dMMR is the “mutant” state, where the MMR channel does not function normally.
For a long time, evaluations of tumor MMR status were mainly carried out in the event of suspicion of Lynch Syndrome, in order to identify patients to be referred to an oncogenetics consultation. But more recent studies have shown that this biomarker is also a predictor of the response to certain immunotherapies in all solid tumors. Cells with more mutations are more likely to be responsive to immunotherapy.
So the researchers distinguished two groups:
- A group categorized by deficient mismatch repair (dMMR);
- A group categorized by competent mismatch repair (pMMR).
70% reduction in risk of disease growth observed
The two groups were treated either with immunotherapy (pembrolizumab or Keytruda already indicated against various cancers) in combination with chemotherapy or with chemotherapy alone.
After 12 months of follow-up, the results appeared:
- The dMMR group showed a 70% reduction in the risk of disease growth (progression-free survival) in participants who received immunotherapy in addition to chemotherapy (74% without tumor progression after 12 months of follow-up versus 34% in the chemotherapy group);
- The pMMR group showed a 46% reduction in the risk of disease growth in participants who received immunotherapy in addition to chemotherapy.
The results are therefore spectacular (even if it concerns non-progression of the disease and not overall survival data), including in patients who do not present a positive predictive factor for immunotherapy.
Limited progress so far in endometrial cancer
Endometrial cancer could become the third most common cancer and the fourth leading cause of cancer death in women by 2040, experts predict, but progress in its treatment has been limited until now. ‘here.
“These results could transform the way we care for patients with advanced or recurrent/advanced uterine cancer. Currently, chemotherapy alone is used in the first-line treatment of patients with this disease”according to Ramez N. Eskander, lead author of the study.
In France too, endometrial cancer is now the fourth leading cause of cancer in women in France and the most common gynecological cancer after breast cancer. It usually affects women after menopause, the average age at diagnosis is 68 years. Symptoms include vaginal bleeding/spotting, pelvic pain, bloating, or changes in bowel or bladder habits. An early diagnosis often giving better results, it is important to consult in case of vaginal bleeding after menopause.
Will we soon see this combination of treatment at work in France? Will the use of such a treatment imply the use of a preliminary test to identify the best responders? Will we have to wait for complete data on overall survival?… The results are such that we can think that practices could change quickly. However, it remains to wait for the green light from the American (Food & Drug Administration) and European (European Medicines Agency EMA – and National Agency for the Safety of Medicines and Health Products – ANSM) medical authorities.
Today, KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced or recurrent endometrial cancer whose disease progresses during or after prior platinum therapy received regardless of whatever the stage and who are not eligible for curative surgery or radiotherapy. These results should allow this drug to benefit from an earlier indication and benefit more women, earlier in their treatment.