Alessandro D. Santin, MD
Adding trastuzumab (Herceptin) to chemotherapy increased progression-free survival (PFS) for patients with advanced HER2/neu-positive uterine serous carcinoma, including those with recurrent disease and patients undergoing primary treatment.
Among all 58 evaluable patients in the phase II trial, the median PFS was 12.6 months with the addition of trastuzumab to carboplatin/paclitaxel, compared with 8.0 months in the control arm of carboplatin/paclitaxel alone (HR, 0.44; 90% CI, 0.26-0.76; P
In a subgroup of 41 patients with stage III/IV disease undergoing primary treatment, the median PFS was 17.9 versus 9.3 months, respectively (HR, 0.40; 90% CI, 0.20-0.80; P
= .013). Among 17 patients with recurrent disease, the median PFS was 9.2 versus 6.0 months, respectively (HR, 0.14; 90% CI, 0.04-0.53; P
“Novel therapeutic strategies must be developed for uterine serous carcinoma. Outcomes for women with this malignancy remain dismal,” wrote corresponding author Alessandro D. Santin, MD, Yale University School of Medicine, and colleagues.
“In this study, we demonstrate that the addition of trastuzumab to carboplatin-paclitaxel in HER2/neu-positive uterine serous carcinoma results in a 56% decrease in risk of progression relative to carboplatin-paclitaxel alone and increases PFS by 4.6 months, with benefit both in first-line adjuvant therapy for advanced-stage disease and in the recurrent setting. A preliminary analysis of OS suggests similar trends, with the most clinical benefit from trastuzumab observed in the upfront treatment setting in those with stage IIIC or IV disease,” added Santin et al.
Sixty-one patients with primary stage III/IV or recurrent HER2/neu-positive disease enrolled in this phase II study from August 2011 to January 2017. Fifty-eight patients were evaluable for PFS. Twenty-eight patients were randomized to the control arm and 30 to the trastuzumab arm.
Forty-one (71%) patients had advanced-stage disease and 17 (29%) had recurrent disease. Twenty-two (54%) of those with advanced-stage disease received primary radiation and 5 (12%) had gross residual disease after primary cytoreductive surgery. Of the patients with recurrent disease, the median number of prior lines of therapy was 1 (range, 0-2) in both treatment arms.
Patients in the control arm completed a total of 156 cycles (range, 1-8) of carboplatin-paclitaxel treatment compared with 178 (range, 4-9) in the experimental arm. Patients in the experimental arm received a total of 519 cycles of trastuzumab (median, 15; range, 5-53).
Among 8 patients with recurrent disease in the control arm, 2 (25%) had complete response as best RECIST response to treatment, 4 (50%) had partial responses, and 1 (12.5%) had stable disease. One patient had progressive disease.
In 9 patients with recurrent disease in the experimental arm, 1 (11%) patient had a complete response, 3 (33%) had partial responses, and 5 (56%) had stable disease. There were no cases of progression. The clinical benefit in the recurrent cohort was 87.5% in the control arm and 100% in the experimental arm (P = .47), with objective response rates of 75% and 44% in the respectively (P
Sixty patients were evaluable for toxicity and 57 experienced at least 1 one adverse event (AE) during treatment. There was no significant difference in grade ≥3 AEs between treatment arms.
Anemia (19%) was the most common (≥5%) grade ≥3 AE in the trastuzumab arm followed by neutropenia (16%), hypertension (16%), decreased neutrophil count (13%), hyperglycemia (9%), decreased white blood cell count (9%), diarrhea, colitis, and enterocolitis (9%); abdominal pain (6%), and hypoxia (6%).
The most common (≥5%) grade ≥3 AEs in the control arm were decreased neutrophil count (18%), anemia (7%), thromboembolic event (7%), and hyponatremia (7%).
Grade 3 hypertension displayed the largest treatment-arm difference, 16% in the trastuzumab arm versus 0% in the control arm (P
= .055). However, of the 5 events recorded, investigators determined that 4 were unrelated or unlikely to be related to trastuzumab, and 1 was possibly related to the study drug.
Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer that represents just 3% to 10% of all diagnoses but accounts for 39% of deaths. The 5-year survival rate for women with uterine serous carcinoma is approximately 41% compared with 75% among women with grade 3 endometrioid tumors (P
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 [published online March 27, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.5966.