Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu
AuthorFader, Amanda N.
Roque, Dana M.
Chambers, Setsuko K.
Secord, Angeles Alvarez
O’Malley, David M.
ElSahwi, Karim S.
Schwartz, Peter E.
Santin, Alessandro D.
MetadataShow full item record
PublisherAMER SOC CLINICAL ONCOLOGY
CitationDOI: 10.1200/JCO.2017.76.5966 Journal of Clinical Oncology 36, no. 20 (July 2018) 2044-2051.
JournalJOURNAL OF CLINICAL ONCOLOGY
Rights© 2018 by American Society of Clinical Oncology
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPurpose 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.
Note6 month embargo; published online: 27 March 2018
VersionFinal published version
SponsorsAbbVie; Amgen; Astellas Pharma; Astex Pharmaceuticals; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Eisai; Endocyte; Exelixis; Incyte; Merck; PharmaMar; Prima BioMed; Genentech; Tesaro; Iovance Biotherapeutics; Agenus; inVentiv Health Clinical; TRACON Pharmaceuticals; Immunogen; Stemcentrx; INC Research; PRA Intl; Janssen Research and Development; Ajinomoto; Clovis Oncology; Serono; ERGOMED Clinical Research; Array BioPharma; Regeneron Pharmaceuticals; BiPar/Sanofi-Aventis
- Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis.
- Authors: Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD
- Issue date: 2020 Aug 1
- Adjuvant Pelvic Radiation "Sandwiched" Between Paclitaxel/Carboplatin Chemotherapy in Women With Completely Resected Uterine Serous Carcinoma: Long-term Follow-up of a Prospective Phase 2 Trial.
- Authors: Frimer M, Miller EM, Shankar V, Girda E, Mehta K, Smith HO, Kuo DYS, Goldberg GL, Einstein MH
- Issue date: 2018 Nov
- Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial.
- Authors: Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, Lara PN Jr, Chatta GS, Nanus DM, Glode LM, Trump DL, Chen H, Smith DC, National Cancer Institute.
- Issue date: 2007 Jun 1
- Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial.
- Authors: Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D
- Issue date: 2015 Jul
- Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes.
- Authors: Fader AN, Nagel C, Axtell AE, Zanotti KM, Kelley JL, Moore KN, Secord AA, Walsh CS, Huh WK, Gehrig PA, Gibbons H, Rose PG, Havrilesky LJ, Tuller E, Drake RD, Bottsford-Miller J, O'Malley DM, UPSC Consortium.
- Issue date: 2009 Mar