Addition of Trastuzumab to Carboplatin/Paclitaxel in HER2-Positive Uterine Serous Carcinoma
In a phase II trial reported in the Journal of Clinical Oncology, Fader et al found that the addition of trastuzumab (Herceptin) to carboplatin/paclitaxel improved progression-free survival among women with HER2-overexpressing uterine serous carcinoma.
HER2 has been found to be overexpressed in approximately 30% of cases of uterine serous carcinoma.
Study Details
In the study, 58 evaluable patients from 11 sites in the U.S. with primary stage III or IV or recurrent HER2-positive disease were randomized between August 2011 and March 2017 to receive carboplatin area under the curve = 5 and paclitaxel 175 mg/m2 over 3 hours every 21 days for 6 cycles with (n = 30) or without (n = 28) trastuzumab at 8 mg/kg for the first dose and 6 mg/kg in subsequent cycles until progression or unacceptable toxicity. Patients may have undergone optimal or suboptimal primary cytoreductive surgery.
The primary endpoint was progression-free survival.
Progression-Free Survival
At time of analysis, at median 10.0 months follow-up, 18 patients remained alive and progression-free, consisting of 13 in the trastuzumab group and 5 in the control group. Median progression-free survival was 12.6 months in the trastuzumab group vs 8.0 months in the control group (hazard ratio [HR] = 0.44, P = .005). Median progression-free survival was 17.9 months vs 9.3 months among 41 patients with stage III or IV disease undergoing primary treatment (HR = 0.40, P = .013) and 9.2 months vs 6.0 months among 17 patients with recurrent disease (HR = 0.14, P = .003).
Adverse Events
The most common grade ≥ 3 adverse events in the trastuzumab group were anemia (19%); hypertension (16%); decreased neutrophils (13%); hyperglycemia (9%); white blood cell decrease (9%); and diarrhea, colitis, or enterocolitis (9%). The most common in the control group were decreased neutrophils (18%), anemia (7%), thromboembolic events (7%), and hyponatremia (7%). One patient in the trastuzumab group had grade 3 decrease in left ventricular ejection fraction. One patient in the control group died from a thromboembolic event.
The investigators concluded, “Addition of trastuzumab to carboplatin/paclitaxel was well tolerated and increased progression-free survival. These encouraging results deserve further investigation to determine their impact on overall survival in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu.”
Alessandro D. Santin, MD, of Yale University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
