Combination of immunotherapy and anti-angiogenesis drug shows potential in form of endometrial cancer in trial

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A combination of two drugs used to treat a form of kidney cancer has shown promise in a clinical trial involving patients with a hard-to-treat type of endometrial cancer, researchers at Dana-Farber Cancer Institute will report at the 2024 Society of Gynecologic Oncology Annual Meeting on Women's Cancer in San Diego today.

The drugs, avelumab and axitinib, exploit different vulnerabilities of endometrial cancer cells. Avelumab is an immune checkpoint inhibitor that exposes tumor cells to an immune system attack; axitinib blocks the growth of blood vessels in tumors and stymies the growth of tumor cells. Together, they're approved as a first-line treatment for patients with advanced renal cell cancer.

In the trial, led by Elizabeth Lee, MD, a medical oncologist in the gynecologic oncology program at Dana-Farber, investigators administered the combination therapy to 35 patients with recurrent or persistent endometrial cancer that was mismatch repair proficient, meaning the tumor cells were able to detect and correct spelling errors in their DNA. All the patients had received at least one prior regimen of chemotherapy.

Of the 35 evaluable patients, 14 achieved a response – a decrease in the extent of their cancer – including two patients with a complete response to the therapy. Responses were seen in patients across all subtypes of endometrial cancer (carcinosarcoma, clear cell, endometrioid, serous) as well as all molecular subtypes.

The median progression-free survival – the length of time patients lived before the cancer worsened – was 7 months. Six months after receiving the therapy, 14 patients were alive with no progression of their cancer.

The avelumab/axitinib pairing is designed to make tumor cells more visible, and vulnerable, to the immune system. Research had shown that the proteins HIF1α and VEGF, which help tumors grow their own blood vessels, also help them stay under the immune system's radar. An earlier combination of a VEGF-blocking drug, lenvatinib, and an immune checkpoint inhibitor, pembrolizumab, was active in endometrial cancer. Experience with avelumab and axitinib in treating patients with advanced renal cell cancer suggested the duo could be more effective and potentially less toxic than lenvatinib and pembrolizumab in patients with mismatch repair–proficient recurrent or persistent endometrial cancer.

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Gynecologic Cancer
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Elizabeth Lee, MD