The addition of trastuzumab to chemotherapy in patients with uterine serous carcinoma had superior outcome compared with chemotherapy alone.
Survival rates were significantly improved with the addition of trastuzumab (Herceptin) to chemotherapy in patients with uterine serous carcinoma (USC), a rare and aggressive form of endometrial cancer. The findings are from a phase 2 trial (NCT01367002) published in Clinical Cancer Research.1,2
“The randomized, multi-institutional phase 2 trial studied 58 women with USC whose tumors expressed high levels of the HER2 protein, which is known to drive several forms of cancer in women,” said Alessandro Santin, MD, professor of gynecology, obstetrics & reproductive sciences, leader of the Disease Aligned Research Team of the Gynecologic Oncology Program at Smilow Cancer Hospital and Yale Cancer Center, and senior study author, in a statement.1
The study explored the use of carboplatin and paclitaxel chemotherapy with or without trastuzumab in patients with advanced or recurrent uterine serous papillary carcinoma who had overexpressed HER2 by immunohistochemistry or fluorescence in situ hybridization.
In the experimental arm, patients received 6 cycles of carboplatin/paclitaxel plus trastuzumab followed by maintenance trastuzumab until disease progression or unacceptable toxicity. The study looked at progression-free survival (PFS) as the primary end point and secondary end points included overall survival (OS) and toxicity.
A total of 61 patients were followed for a median of 25.9 months. According to the updated survival results, the median PFS achieved with trastuzumab plus chemotherapy was 12.9 months compared with 8.0 months in the control arm (HR, 0.46; 90% CI, 0.28-0.76; P = .005). In the subset of 41 patients with stage III to IV disease who were treatment-naïve, the median PFS was 17.7 months with the trastuzumab combination versus 9.3 months with the control treatment (HR, 0.44; 90% CI, 0.23-0.83; P = .015). Finally, in the recurrent disease subgroup, the median PFS was 9.2 with the addition of trastuzumab to chemotherapy versus 9.2 months with the control (HR, 0.12; 90% CI, 0.03-0.48; P = .004).2
Overall survival also favored the trastuzumab/chemotherapy arm. The median OS was 29.6 months with trastuzumab and chemotherapy versus 24.4 months with the control (HR,0.58; 90% CI, 0.34-0.99; P = .046). Among treatment-naïve patients with stage III to IV disease, the benefit of trastuzumab/chemotherapy was most evident as the median OS was not yet reached versus 24.4 months (HR, 0.49; 90% CI, 0.25-0.97; P = .041).
The safety analysis showed that trastuzumab was well tolerated in patients, said Santin. Also, both treatment arms demonstrated similar toxicity.
Preclinical research around the combination of trastuzumab and chemotherapy ultimately led tochanges in the National Comprehensive Cancer Network (NCCN) guidelines in 2018. The NCCN now recommend this combination for the treatment of patients with HER2-positive USC.
“With the revision of the 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.
1. Yale cancer center study validates combination therapy for aggressive endometrial cancer. News release. Yale cancer center. June 29, 2020. Accessed June 30, 2020. https://bit.ly/3gbqcoy
2. 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. Published online June 29, 2020. doi:10.1158/1078-0432.ccr-20-0953