This type of cancer occurs when cells that line the uterus mutate, and as a result, multiply. While surgery is a common treatment for early-stage endometrial cancer, it is not the case for advanced forms of the disease. That’s why new treatment approvals are needed to help patients suffering from this condition.

In this article, we look at the latest therapies recently approved and those currently in development for the treatment of endometrial cancer.

Checkpoint inhibitors have been climbing the regulatory ladder this year when it comes to endometrial cancer. These drugs are a kind of immunotherapy that block proteins called checkpoints that prevent immune cells from killing cancer by sending an ‘off signal.’. 

Expanded FDA approval of Jemperli brings new treatment options for recurrent endometrial cancer patients

In August, the FDA expanded the approval of GSK’s Jemperli in combination with chemotherapy to all patients with primary advanced or recurrent endometrial cancer, which means that patients with mismatch repair–proficient (pMMR) – a patient cohort that was left out in its 2021 approval – can also be treated with the drug.

Jemperli works by binding to the PD-1 receptor so that the latter cannot interact with PD-L1 and PD-L2 – proteins expressed in tumor cells – and aiding an anti-tumor immune response. In a phase 3 trial, there was a 40% decline in the risk of disease progression or death in patients with recurrent endometrial cancer.  According to Dr. Mona S. Jhaveri, founder of Music Beats Cancer, a charitable crowdfunding platform that supports innovation in oncology, recurrence is a major unmet need for patients with endometrial cancer, so these drug approvals hold a lot of value. But Jhaveri also explained that ways to diagnose recurrence more quickly must be improved.

“Doctors will monitor patients with follow up exams that include pap smears and imaging. However, survival after recurrence is rarely more than two years. We need better ways to screen for this risk,” said Jhaveri.

While Jemperli’s expanded FDA approval came last month, the National Health Service (NHS) in the U.K. began its rollout in March. Around 150 to 200 women living with endometrial cancer in the U.K. will be eligible each year.

“The rollout of this drug as a first-line treatment on the NHS is great news for patients living with this type of womb cancer. This new immunotherapy could offer hundreds of women the hope of precious extra time to live well before their cancer progresses,” said Peter Clark, NHS England’s Cancer Drugs Fund Lead, in a press release.

AstraZeneca’s Lynparza-Imfinzi combination gains EU approval for advanced endometrial cancer treatment

Also last month, British multinational AstraZeneca’s combination of two drugs, Lynparza and Imfinzi, snagged the greenlight from the European Union (EU) to treat patients with primary advanced or recurrent endometrial cancer. Imfinzi and chemotherapy followed by the Lynparza-Imfinzi combination was approved for mismatch repair proficient (pMMR) disease – a type of cancer where MMR proteins are expressed normally. Imfinzi plus chemotherapy followed by Imfinzi alone was cleared for deficient MMR (dMMR) – when MMR proteins are not expressed.

This was based on a phase 3 trial where a 43% reduction in the risk of pMMR disease progression or death for patients on the Lynparza and Imfinzi regimen was observed whereas there was a Imfinzi 58% decrease in the Imfinzi regimen in patients with dMMR endometrial cancer. Lynparza is a PARP inhibitor meaning that it stops the poly ADP-ribose polymerase (PARP) enzyme from doing its repair work in cancer cells and ultimately allowing the cells to die. Imfinzi, like Jemperli, is a checkpoint inhibitor.

“In the case of many cancers, these checkpoints prevent T cells from killing cancer cells,” said Jhaveri. “These approvals are significant because it marks the first-ever approval for a combination of immunotherapies and a PARP inhibitor, which is a major step forward for patients with endometrial cancer.”

The Lynparza-Imfinzi combination could significantly affect thousands of women with defects in the DNA repair process. Earlier this year, an Imfinzi-chemotherapy regimen was given the U.S. Food and Drug Administration (FDA) nod in patients with dMMR endometrial cancer. 

Merck’s Keytruda receives expanded approval for treating all forms of advanced endometrial cancer

Another checkpoint inhibitor that has bagged expanded approval to combat all forms of advanced endometrial cancer is pharma giant Merck’s Keytruda. The drug has been on the market for almost a decade since it was first cleared to treat advanced skin cancer. Like Jemperli, it was also authorized in 2021 to treat certain endometrial cancers, but not all. This year’s approval for Keytruda in combination with chemotherapy marks progress in endometrial cancer care as well as checkpoint inhibitor research.

These medicines “can be used to effectively treat certain endometrial tumors that have defects in the DNA repair process,” explained Dr. Joshua G. Cohen, medical director of the Gynecologic Cancer Program at City of Hope Orange County in Irvine, California.

“These new treatment combinations are important because they appear to improve outcomes for certain patients with specific molecular alterations who have advanced or recurrent endometrial cancer,” said Cohen.

Another advancement in endometrial cancer research is the development of antibody drug conjugates (ADCs) that are “designed to attack tumor cells with specific receptors,” according to Cohen. “An example of this is the HER2 target for patients with tumor cells that highly express this receptor.”

ADCs consist of a monoclonal antibody that is bound to a linker that links it to a drug – typically a chemotherapy. These drugs bind to proteins in cancer cells where the chemotherapy is released for a more targeted approach. Although no ADC has been approved for endometrial cancer, several have been backed to treat solid tumors like breast cancer. This includes trastuzumab-deruxtecan, known by its brand name Enhertu, which secured the FDA’s stamp of approval this year to treat HER2-positive solid tumors.

Enhertu’s promise in endometrial cancer is one to look out for. The AstraZeneca and Daiichi Sankyo-owned drug had an 84.6% overall response rate and progression-free and overall survival of patients with endometrial cancer were 11.1 months and 26 months, respectively.

Besides Enhertu, American pharmaceutical ImmunoGen’s ADC Elahere is also being tested in endometrial cancer. The treatment met its primary endpoint in a phase 2 trial where 37.5% of patients achieved an objective response. One patient had a complete response and five other patients had a partial response. The therapy was recently given the FDA go-ahead to treat certain ovarian cancers.

With ADCs in the spotlight, BioNTech and DualityBio’s drug BNT323/DB-1303 which targets HER-2 in endometrial cancer, secured Breakthrough Therapy designation from the FDA late last year and a phase 3 trial is much-awaited.

Apart from these landmark approvals and ADC clinical trials, Cohen believes that a major breakthrough in therapeutic research is the Cancer Genome Atlas’ discovery of the different subtypes of the disease – POLE-mutated, MMRd, no specific molecular profile, and p53 abnormal – based on genetic and molecular features. 

“[This] is clinically significant in that the subtypes have different likelihoods of recurrence. Physicians can now implement a treatment plan that is even more personalized to the individual patient, depending on which subtype the patient has,” said Cohen.

“An unmet need for patients with endometrial cancer has been to manage the disease effectively beyond the standard treatments for an early-stage diagnosis – surgery, chemotherapy or radiation. Now, with the identification of endometrial tumor subtypes and new immunotherapy combinations, this need is being addressed and patients are benefiting. There are new drug combinations being tested for those patients who are not candidates for immunotherapy or the tumor is progressing despite use of immunotherapy.”

As checkpoint inhibitors continue to ride the approval wave, ADCs in the clinic could also do the same a few years from now and broaden therapeutic approaches for endometrial cancer.