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Addition of Trastuzumab to Carboplatin/Paclitaxel for Advanced or Recurrent HER2-Positive Uterine Serous Carcinoma


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Combining the HER2-targeted therapy trastuzumab with carboplatin and paclitaxel improved survival rates for women with a rare, aggressive type of endometrial cancer, according to findings published by Amanda N. Fader, MD, of Johns Hopkins School of Medicine, Baltimore, and colleagues in Clinical Cancer Research.1 Each year, more than 65,650 women in the United States are diagnosed with endometrial cancer, and more than 12,590 die of the disease.

Amanda N. Fader, MD

Amanda N. Fader, MD

Alessandro Santin, MD

Alessandro Santin, MD

“As this country’s population ages and obesity climbs, these numbers are likely to double in the next decade,” said senior study author Alessandro Santin, MD, Professor of Gynecology, Obstetrics and Reproductive Sciences and Leader of the Disease Aligned Research Team of the Gynecologic Oncology Program at Smilow Cancer Hospital and Yale Cancer Center, in a statement. “Uterine serous carcinoma accounts for only 3% to 10% of all these cases of endometrial cancer, but it kills over 40% of the patients because it’s so aggressive.”

Study Methods

“The randomized, multi-institutional phase II trial studied 58 women with uterine serous carcinoma whose tumors expressed high levels of the HER2 protein, which is known to drive several forms of cancer in women,” said Dr. Santin.

After surgery, women with either stage III or IV disease were randomly assigned to treatment with the chemotherapy regimen of carboplatin and paclitaxel for six cycles or the same combination chemotherapy regimen followed by trastuzumab. The primary study endpoint was progression-free survival.

Results

Average progression-free survival almost doubled, from 9.3 months in the control arm to 17.7 months in the trastuzumab arm, among 41 patients with stage III to IV disease undergoing primary treatment and from 7.0 months to 9.2 months among 17 patients with recurrent disease. Overall survival benefit was most notable in women with stage III to IV disease, with median survival not reached in those given trastuzumab vs 24.4 months in the control group.

“Importantly, the trial showed no difference in toxicity between the two groups,” added Dr. Santin.

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

The study authors concluded: “Addition of trastuzumab to carboplatin/paclitaxel increased progression-free survival and overall survival in women with advanced/recurrent HER2-positive uterine serous carcinoma, with the greatest benefit seen for the treatment of stage III to IV disease.” 

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.

Reference

1. Fader AN, Roque DM, Siegel E, et al: Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III–IV) or recurrent uterine serous carcinomas that overexpress HER2/neu (NCT01367002): Updated overall survival analysis. Clin Cancer Res 26:3928-3935, 2020.

 


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