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Drug combo may extend the lives of women with advanced endometrial cancer

Two new studies find that adding immunotherapy to standard chemotherapy lengthens the time before tumors return.

Women with advanced endometrial cancer may live longer before their tumors return if they receive immunotherapy and chemotherapy at the same time, according to two studies published Monday in the New England Journal of Medicine.

The findings, which were also presented Monday at the annual meeting of the Society of Gynecologic Oncology in Tampa, Florida, are expected to transform the way cancer doctors treat women in later stages of their disease.

"This is going to drastically change the conversation" with patients — "probably as of tomorrow," said Dr. David O'Malley, a gynecologic oncologist with The Ohio State University Comprehensive Cancer Center. O'Malley was not involved with the new studies.

In one of the studies, researchers found that adding the immunotherapy drug pembrolizumab (commonly known by its brand name, Keytruda) to the standard chemotherapy regimen of carboplatin and paclitaxel reduced the risk that patients' advanced or recurrent endometrial cancer would return by up to 70%, depending on the types of tumors they had.

"We found a profound improvement," said senior study author Dr. Carol Aghajanian, a medical oncologist specializing in gynecologic cancers at Memorial Sloan Kettering Cancer Center in New York City.

Some patients in the study who received the combination treatment went, on average, more than a year (13.1 months) before their disease progressed, compared to 8.7 months, on average, among those who only got chemotherapy.

The impact was more dramatic in women with a mismatch repair-deficient tumor, a specific type of endometrial cancer.

While women in the chemo-only group went, on average, 7.6 months before their cancer progressed, women with the mismatch repair-deficient tumor type that got chemotherapy plus immunotherapy are doing so well a year later, that not enough have had tumor progression to allow researchers to determine how long the benefits might last.

Dr. Pamela Soliman, a gynecologic oncologist at MD Anderson Cancer Center in Houston who was not involved in the new studies, said the findings were exciting.

"Patients with either advanced or recurrent endometrial cancer don’t have a lot of great treatment opportunities," Soliman said. "This is really practice-changing."

Currently, immunotherapy is only approved for endometrial cancer as a second line of treatment, after chemotherapy. These findings suggest a significant advantage to using immunotherapy as part of the first line of treatment in these advanced cancers.

The Food and Drug Administration would need to amend its guidance on using immunotherapy in this way before it's widely implemented as the protocol for treating late-stage endometrial cancer. Aghajanian said regulators are already reviewing the new data.

Women are not screened for endometrial cancer. Instead, it's typically detected when symptoms develop. The most common symptoms include post-menopausal bleeding or other irregular vaginal bleeding.

The American Cancer Society estimates that 66,200 cases of endometrial cancer will be diagnosed this year, and more than 13,000 women will die of the disease.

Rates of new endometrial cancers has risen 0.6% per year from 2010 to 2019, according to the National Cancer Institute.

A second study published Monday compared chemotherapy with a chemo-combination therapy that included a monoclonal antibody called dostarlimab.

Again, depending on the type of endometrial tumor, the risk that the cancer would return was reduced by up to 61.4% for up to two years after treatment.

Both studies were welcomed by clinicians frustrated by rising endometrial cancer cases.

"Endometrial cancer is one of the few cancers that is rising, increasing in mortality in the United States," said Aghajanian. "Unfortunately, very few treatments have been developed specifically for it."

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