Study Validates Combination Therapy for Aggressive Endometrial Cancer

Newswise — Yale Cancer Center (YCC) scientists have found that combining the targeted drug trastuzumab with chemotherapy significantly improves survival rates for women with a rare, aggressive form of endometrial cancer. These results may help to change the standard of care worldwide for the disease. The findings are published today in the journal Clinical Cancer Research.

“The randomized, multi-institutional phase 2 trial studied 58 women with uterine serous carcinoma (USC) whose tumors expressed high levels of the HER2 protein, which is known to drive several forms of cancer in women,” said Alessandro Santin, M.D., Professor of Gynecology, Obstetrics & Reproductive Sciences, Leader of the Disease Aligned Research Team of the Gynecologic Oncology Program at Smilow Cancer Hospital and YCC, and senior author of the study. After surgery, women were either given a standard chemotherapy regimen of carboplatin and paclitaxel, or the same combination chemotherapy regimen followed by trastuzumab. Trastuzumab targets HER2, a surface receptor, and has long improved outcomes for many women whose breast cancers display high levels of HER2 expression.

The combination therapy with trastuzumab was particularly effective among 41 women with advanced stage 3 and stage 4 USC receiving their first treatment for the disease. Average progression-free survival (PFS) doubled from about 9 months in the control arm to 18 months in women given the treatment, “which is unprecedented for this cancer,” Santin said.

“Importantly, the trial showed no difference in toxicity between the two groups,” said Santin. “Trastuzumab is a humanized antibody, a natural product of our bodies, and it is extremely well tolerated.”

Each year, more than 65,650 women in the United States are diagnosed with endometrial cancer, and over 12,590 die of the disease. “As this country’s population ages and obesity climbs these numbers are likely to double in the next decade,” said Santin. “USC accounts for only three to ten percent of all these cases of endometrial cancer, but it kills over 40% of the patients because it’s so aggressive,” he added.

Among the 17 women in the study where USC recurred, the combination treatment prolonged the disease-free interval but did not significantly improve survival when compared to the standard chemotherapy regimen. “These are patients who return with large amounts of metastatic cancer,” Santin said. “Most likely their tumor burden is so high and heterogenous that the tumor becomes resistant also to trastuzumab.”

Back in 2018, after examining preliminary data on the phase 2 trial, the National Comprehensive Cancer Network (NCCN) adopted the chemotherapy/trastuzumab combination for new treatment of women with HER2-positive USC as a guideline for treatment. NCCN is widely recognized by both clinicians and payers as the U.S. standard-setting body for oncology clinical guidelines.  “With those NCCN guidelines, everybody started using it,” Santin said. Now that the final results for the trial are published, he expects much broader worldwide adoption of the combination.

Amanda Fader, M.D., was first author on the paper. Yale’s Natalia Buza, M.D., Pei Hui, M.D., Ph.D., Osama Abdelghany, Stefania Bellone, Ph.D., Masoud Azodi, M.D., Elena Ratner, M.D., Dan-Arin Silasi, M.D., and Peter Schwartz, M.D., contributed to the study.

Roche’s Genentech subsidiary provided funding for the research.

About Yale Cancer Center and Smilow Cancer Hospital Yale Cancer Center (YCC) is one of only 51 National Cancer Institute (NCI)-designated comprehensive cancer centers in the nation and the only such center in Connecticut. Cancer treatment for patients is available at Smilow Cancer Hospital through 13 multidisciplinary teams and at 15 Smilow Cancer Hospital Care Centers in Connecticut and Rhode Island. Smilow Cancer Hospital is accredited by the Commission on Cancer, a Quality program of the American College of Surgeons. Comprehensive cancer centers play a vital role in the advancement of the NCI’s goal of reducing morbidity and mortality from cancer through scientific research, cancer prevention, and innovative cancer treatment.

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