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Combining Immunotherapy and Chemotherapy Reduces Endometrial Cancer Growth

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Endometrial cancer is most common in post-menopausal women, and vaginal bleeding/spotting in this patient population can sometimes be overlooked. Symptoms of endometrial cancer include vaginal bleeding/spotting, pelvic pain, bloating, or change in bowel or bladder habits.

The immunotherapy drug used is pembrolizumab, which is a monoclonal antibody that targets the programmed cell death protein 1 (PD-1) receptor on immune cells. By blocking this receptor, pembrolizumab prevents cancer cells from evading the immune system and allows the immune system to recognize and attack the cancer cells.

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Chemotherapy, on the other hand, involves the use of drugs that target rapidly dividing cells, including cancer cells. Chemotherapy drugs work by damaging DNA in rapidly dividing cells, which prevents the cells from dividing and eventually leads to cell death.

Combining pembrolizumab with chemotherapy is thought to enhance the immune system’s ability to recognize and attack cancer cells, while also directly targeting the cancer cells with chemotherapy. This combination approach has shown promising results in treating various types of cancer, including endometrial cancer.

Dr. Ramez N. Eskander, the principal investigator and lead author of the study, stated that the combination therapy “may transform the way we care for patients with advanced stage or recurrent/advanced uterine cancer,” as chemotherapy alone is currently the first-line treatment for patients with this disease.

“It is critical that we work to identify effective and innovative treatments and combination therapies, such as immunotherapy and chemotherapy, to attack this cancer and give patients more time to live their lives fully,” added Dr. Eskander, an associate professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at UC San Diego School of Medicine.

Combining Immunotherapy and Chemotherapy: Trials and Results

The Phase III trial was a blinded, placebo-controlled, randomized study involving 816 people with Stage III or IV endometrial cancer. The participants were assigned to two groups, deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR), and treated with either immunotherapy in combination with chemotherapy or with chemotherapy alone.

Mismatch repair (MMR) proteins describe cells that have mutations in certain genes that are involved in correcting mistakes made when DNA is copied in a cell. In the “normal” state, our cells are in pMMR, where the MMR pathway is active and functional. In the “mutant” state, cells are in dMMR, where the MMR pathway is not working as usual.

After a follow-up time of 12 months, the dMMR group showed a 70% reduction in the risk of disease growth in the participants who received immunotherapy in addition to chemotherapy, while the pMMR group showed a 46% reduction in the risk of disease growth in the participants who received immunotherapy in addition to chemotherapy.

Supporting Evidence for Newer Drugs for Endometrial Cancer

A 2021 study published in the Journal of Clinical Oncology found that adding immunotherapy to chemotherapy improved progression-free survival and overall survival in patients with recurrent or metastatic endometrial cancer.

A 2020 study published in the Journal of Gynecologic Oncology found that combination therapy with pembrolizumab and chemotherapy improved objective response rates and progression-free survival in patients with advanced endometrial cancer.

A 2019 study published in the European Journal of Cancer found that pembrolizumab, an immunotherapy drug, demonstrated promising results in patients with advanced or recurrent endometrial cancer.

A 2018 study published in the Journal of Gynecologic Oncology found that patients with mismatch repair-deficient endometrial cancer had a higher response rate to immunotherapy with pembrolizumab compared to patients with mismatch repair-proficient endometrial cancer.

A 2017 study published in the Journal of Clinical Oncology found that pembrolizumab demonstrated a durable response and manageable safety profile in patients with advanced endometrial cancer.

Dr. Eskander emphasized the importance of early diagnosis, stating that anyone experiencing vaginal bleeding, even spotting, when post-menopausal should speak to their doctor.

The next steps to further the study results are to receive approval from the Food & Drug Administration and implement the new treatment approach as a standard practice.

Overall, this study represents a significant advancement in the treatment of endometrial cancer and may lead to improved outcomes for patients with this disease.

Source: Medindia

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