Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu

Amanda N. Fader, Dana M. Roque, Eric Siegel, Natalia Buza, Pei Hui, Osama Abdelghany, Setsuko K. Chambers, Angeles Alvarez Secord, Laura Havrilesky, David M. O'Malley, Floor Backes, Nicole Nevadunsky, Babak Edraki, Dirk Pikaart, William Lowery, Karim S. El Sahwi, Paul Celano, Stefania Bellone, Masoud Azodi, Babak LitkouhiElena Ratner, Dan Arin Silasi, Peter E. Schwartz, Alessandro D. Santin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2044-2051
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number20
DOIs
StatePublished - Jul 10 2018

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Carboplatin
Paclitaxel
Carcinoma
Disease-Free Survival
ErbB-2 Receptor
Antibodies, Monoclonal, Humanized
Endometrial Neoplasms
human ERBB2 protein
Trastuzumab
Therapeutics
Safety
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. / Fader, Amanda N.; Roque, Dana M.; Siegel, Eric; Buza, Natalia; Hui, Pei; Abdelghany, Osama; Chambers, Setsuko K.; Secord, Angeles Alvarez; Havrilesky, Laura; O'Malley, David M.; Backes, Floor; Nevadunsky, Nicole; Edraki, Babak; Pikaart, Dirk; Lowery, William; El Sahwi, Karim S.; Celano, Paul; Bellone, Stefania; Azodi, Masoud; Litkouhi, Babak; Ratner, Elena; Silasi, Dan Arin; Schwartz, Peter E.; Santin, Alessandro D.

In: Journal of Clinical Oncology, Vol. 36, No. 20, 10.07.2018, p. 2044-2051.

Research output: Contribution to journalArticle

Fader, AN, Roque, DM, Siegel, E, Buza, N, Hui, P, Abdelghany, O, Chambers, SK, Secord, AA, Havrilesky, L, O'Malley, DM, Backes, F, Nevadunsky, N, Edraki, B, Pikaart, D, Lowery, W, El Sahwi, KS, Celano, P, Bellone, S, Azodi, M, Litkouhi, B, Ratner, E, Silasi, DA, Schwartz, PE & Santin, AD 2018, 'Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu', Journal of Clinical Oncology, vol. 36, no. 20, pp. 2044-2051. https://doi.org/10.1200/JCO.2017.76.5966
Fader, Amanda N. ; Roque, Dana M. ; Siegel, Eric ; Buza, Natalia ; Hui, Pei ; Abdelghany, Osama ; Chambers, Setsuko K. ; Secord, Angeles Alvarez ; Havrilesky, Laura ; O'Malley, David M. ; Backes, Floor ; Nevadunsky, Nicole ; Edraki, Babak ; Pikaart, Dirk ; Lowery, William ; El Sahwi, Karim S. ; Celano, Paul ; Bellone, Stefania ; Azodi, Masoud ; Litkouhi, Babak ; Ratner, Elena ; Silasi, Dan Arin ; Schwartz, Peter E. ; Santin, Alessandro D. / Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 20. pp. 2044-2051.
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title = "Randomized Phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu",
abstract = "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.",
author = "Fader, {Amanda N.} and Roque, {Dana M.} and Eric Siegel and Natalia Buza and Pei Hui and Osama Abdelghany and Chambers, {Setsuko K.} and Secord, {Angeles Alvarez} and Laura Havrilesky and O'Malley, {David M.} and Floor Backes and Nicole Nevadunsky and Babak Edraki and Dirk Pikaart and William Lowery and {El Sahwi}, {Karim S.} and Paul Celano and Stefania Bellone and Masoud Azodi and Babak Litkouhi and Elena Ratner and Silasi, {Dan Arin} and Schwartz, {Peter E.} and Santin, {Alessandro D.}",
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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.

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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