TY - JOUR
T1 - Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu
AU - Fader, Amanda N.
AU - Roque, Dana M.
AU - Siegel, Eric
AU - Buza, Natalia
AU - Hui, Pei
AU - Abdelghany, Osama
AU - Chambers, Setsuko K.
AU - Secord, Angeles Alvarez
AU - Havrilesky, Laura
AU - O'Malley, David M.
AU - Backes, Floor
AU - Nevadunsky, Nicole
AU - Edraki, Babak
AU - Pikaart, Dirk
AU - Lowery, William
AU - El Sahwi, Karim S.
AU - Celano, Paul
AU - Bellone, Stefania
AU - Azodi, Masoud
AU - Litkouhi, Babak
AU - Ratner, Elena
AU - Silasi, Dan Arin
AU - Schwartz, Peter E.
AU - Santin, Alessandro D.
N1 - Publisher Copyright:
© 2018 by American Society of Clinical Oncology.
PY - 2018/7/10
Y1 - 2018/7/10
N2 - Purpose: Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods: Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results: From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival-related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment (P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease (P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion: 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.
AB - Purpose: Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods: Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results: From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival-related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment (P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease (P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion: 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.
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U2 - 10.1200/JCO.2017.76.5966
DO - 10.1200/JCO.2017.76.5966
M3 - Article
C2 - 29584549
AN - SCOPUS:85049746228
SN - 0732-183X
VL - 36
SP - 2044
EP - 2051
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -