|The following article features coverage from the Society of Gynecologic Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Long-term follow-up of a phase 2 trial evaluating the safety and efficacy of platinum-based chemotherapy with and without trastuzumab in women with advanced uterine serous carcinoma showed an overall survival benefit for the addition of HER2-targeted therapy. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.
Approximately 30% of uterine serous carcinomas are characterized by overexpression of HER2, thereby raising the possibility of benefit from treatment with HER2-targeted agents such as trastuzumab.
In this open-label, randomized, phase 2 trial, combination chemotherapy with carboplatin plus paclitaxel with or without trastuzumab was evaluated as first-line adjuvant therapy in patients with stage III/IV HER2-positive uterine serous carcinoma or as initial therapy in those with recurrent HER2-positive disease (ClinicalTrials.gov Identifier: NCT01367002). The primary study endpoint was progression-free survival (PFS), with secondary study endpoints including safety and overall survival (OS).
Results of an earlier analysis of the study data, conducted at a median follow-up of 10 months, showed that of the 58 evaluable patients who underwent random assignment, PFS was significantly improved in those who received trastuzumab. Toxicity was similar in the 2 study arms.2
In this analysis, performed at a median follow-up of 25.9 months, PFS remained significantly longer for the patients receiving trastuzumab. For the overall group, median PFS was 12.9 and 8.0 months for those treated with and without trastuzumab, respectively (hazard ratio [HR], 0.46; 90% CI, 0.28-0.76; P= 0.005).
When the subgroups of patients receiving first-line treatment for primary stage III/IV disease (41 patients) and those receiving initial therapy for recurrent disease (17 patients) were analyzed separately, median PFS for those treated with and without trastuzumab were 17.7 months and 9.3 months for those with primary stage III/IV disease (HR, 0.44; 95% CI, 0.23-0.83; P =.015), and 9.2 months and 7.0 months for those with recurrent disease (HR, 0.12; 90% CI, 0.03-0.48; P =.004).1
Perhaps the most striking results of this analysis pertain to OS. The median OS was 29.6 months for those receiving trastuzumab compared with 24.4 months for those in the control arm, and this difference was statistically significant (HR, 0.58; 90% CI, 0.34-0.99; P =.046).1
The OS survival benefit of trastuzumab was particularly evident in the subgroup of patients receiving first-line adjuvant therapy for stage III/IV disease, with a median OS of not reached and 25.4 months for those treated with and without trastuzumab (HR, 0.49; 90% CI, 0.25-0.97; P =.041). In contrast, a comparison of median OS for the subgroup of patients with recurrent disease did not show a significant difference for those patients treated with trastuzumab vs those who were not.1
Finally, no new safety signals were observed with addition of trastuzumab to chemotherapy with longer follow-up.
Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.
- Fader AN, Roque DM, Siegel ER, et al. Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxed-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/neu: updated survival analysis. Submitted to: Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer. Abstract 12.
- Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018;36:2044-2051.