ADDITION OF TRASTUZUMAB FOR HER2+ SEROUS UTERINE 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/m²over 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.