Expert Talks Differences Between Recent FDA-Approved Endometrial Cancer Therapies

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For patients with endometrial cancer that is dMMR, the two new drug approvals lead to more options, with a new option for patients with pMMR disease, too.

Image of FDA approval, what you need to know.

The FDA's approval of Imfinzi plus chemotherapy and Keytruda plus chemotherapy address a significant unmet needs.

The recent Food and Drug Administration (FDA) approvals of Imfinzi (durvalumab) plus chemotherapy as well as Keytruda (pembrolizumab) plus chemotherapy for patients with endometrial cancer “increases options for patients,” an expert told CURE®.

In mid-June, the FDA approved two new treatment combinations for patients with endometrial cancer. Imfinzi added to chemotherapy was approved for patients with advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR; a mutation interferes with how cells copy their DNA). Additionally, Keytruda added to chemotherapy was approved for patients with advanced endometrial cancers that are dMMR or mismatch repair proficient (pMMR).

In 2023, the FDA approved Jemperli (dostarlimab) with chemotherapy for patients with advanced or recurrent endometrial cancer that is dMMR or microsatellite instability-high (cancer cells with many mutations within the microsatellites). Now these two new approvals open the floor for “improved disease control,” Dr. Angeles Secord, a gynecologic oncologist at Duke Cancer Center, said in an interview with CURE®.

Imfinzi Plus Chemotherapy in dMMR Endometrial Cancer

With the approval of Imfinzi added to chemotherapy to treat patients with dMMR endometrial cancer, Secord explained that it offers new options for patients.

“The importance here is that there’s already an approval for another drug called [Jemperli] immunotherapy with chemotherapy in this setting,” she said. “What the most recent FDA approval [of Imfinzi with chemotherapy] allows is yet another immunotherapy drug that can be combined with chemotherapy for patients with primary cancer recurrent individual cancer that is characterized by mismatch repair deficiency. So, adding additional drugs into this very important clinical arena increases options for patients.”

She emphasized that “approximately 100,000 women around the world die of uterine malignancies,” so having these FDA approvals for endometrial cancer is essential.

“The rising incidence of uterine cancers and the mortality rates are very disconcerting and alarming,” Secord said. “It has been a call for action now for years, so any [FDA] approval of therapies is incredibly important, and the addition of this immunotherapy adds to that.”

WATCH: Keytruda Combo Beneficial ‘Irrespective of PD-L1’ in Endometrial Cancer

Keytruda Plus Chemotherapy in pMMR and dMMR Endometrial Cancers

Based on the National Comprehensive Cancer Network (NCCN) guidelines, Secord noted that there was widespread use of Keytruda plus chemotherapy in the dMMR population.

“This [Keytruda-plus-chemotherapy approval] is incredibly important because previously, the approvals were limited to patients with deficient mismatch repair disease,” Secord explained. “This expands the access to treatment for patients beyond mismatch repair deficiency to include those with mismatch proficient cancers, and that’s a substantial percentage of patients that fall into this category.”

Of note, Secord mentioned that the KEYNOTE-868/NRG-GY018 study helped assess “the relative benefit of adding immunotherapy” in two groups separately: patients with dMMR and patients with pMMR disease.

“While the magnitude of benefit may not be as great in these patients with cancers that are characterized by proficient mismatch repair, it still demonstrated improvement and overall outcomes that are important to take into consideration,” she said. “As a physician, when I'm having these conversations with my patients, I'm able to say to them, ‘Your improvement in disease control is going to be a 40% reduction in disease progression if we can add [Keytruda] to your treatment,’ and put that in the context of the side effects and help patients make decisions that are best for them.”

The Differences Between Imfinzi Plus Chemotherapy and Keytruda Plus Chemotherapy

Key differences between the way these two treatment combinations work are based on the different proteins they target, Secord said.

Specifically, Imfinzi is a PD-L1 inhibitor, which targets the PD-L1 protein found on cancer cells. When the PD-L1 protein on cancer cells attaches to the PD-1 protein on immune cells, it tells the immune system not to attack the cancer, according to the American Cancer Society.

Keytruda, on the other hand, is a type of immunotherapy that binds to PD-1 and blocks the binding to PD-L1 in order to destroy cancer cells.

“It’s not really certain if there’s a difference in activity based on these two different mechanisms of action,” Secord clarified. “It’s just wonderful that there are three drugs that are now available to patients.”

For now, the combination of Keytruda and chemotherapy is currently the only option for patients whose endometrial cancer is pMMR, Secord said. Patients with dMMR disease now have access to Imfinzi plus chemotherapy, Keytruda plus chemotherapy and Jemperli plus chemotherapy.

Knowing Which Treatment Is Right for dMMR Endometrial Cancer

Unfortunately, decisions on which drugs to use for dMMR endometrial cancer may not be the same for everyone, especially because it depends on factors, such as the doctor’s comfort with certain drugs, Secord explained.

“How [patients’] doctors make that decision is going to vary based on the location of where they practice,” she said. “Perhaps based on the treating physicians’ understanding of the clinical trials or their comfort with one specific drug or the other, and perhaps in part on patient preferences.”

So, Secord advised patients to talk with their doctor to see what the best fit may be.

“[Patients should] talk to [their] doctors about the importance of biomarker testing to better understand the overall prognosis [and] if [they’re] at risk or [their] family is at risk for an inherited cancer syndrome,” she said. “[Also,] how much [they will] benefit from an immunotherapy and make sure [they] have a discussion with [their doctors] about adding immunotherapy to [their] chemotherapy for treatment of these diseases.”

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