TY - JOUR
T1 - 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)
T2 - Updated Overall Survival Analysis
AU - Fader, Amanda N.
AU - Roque, Dana M.
AU - Siegel, Eric
AU - Buza, Natalia
AU - Hui, Pei
AU - Abdelghany, Osama
AU - Chambers, Setsuko
AU - Secord, Angeles Alvarez
AU - Havrilesky, Laura
AU - O'Malley, David M.
AU - Backes, Floor J.
AU - Nevadunsky, Nicole
AU - Edraki, Babak
AU - Pikaart, Dirk
AU - Lowery, William
AU - ElSahwi, Karim
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 - Funding Information:
A. Alvarez Secord reports grants from AbbVie, Amgen, Astellas Pharma Inc., Astex Pharmaceuticals Inc, Boehringer Ingelheim, Bristol Myers Squibb, Clovis (honorarium for advisory board), Eisai, Endocyte, Exelixis, Immutep Ltd, Incyte, PharmaMar, Seattle Genetics, Inc., VBL Therapeutics, and National Cancer Trial Network; grants and personal fees from AstraZeneca (honorarium for advisory board), Merck (honorarium for advisory board), Roche/Genentech (honorarium for advisory board), Tesaro/GSK (honorarium for advisory board); personal fees from Aravive (honorarium for advisory board), Cordgenics (honorarium for advisory board), Eisai (honorarium for advisory board), Janssen/Johnson & Johnson (honorarium for advisory board), Mersana (honorarium for advisory board), Myriad (honorarium for advisory board), Oncoquest (honorarium for advisory board); other from GOG Board of Directors (board member) outside the submitted work; and reports being a Steering Committee member for the OVAL trial (VBL Therapeutics) and the AtTend trial (Roche/Genentech), noncompensated and not relevant to submitted work. L. Havrilesky reports grants from AstraZeneca and Tesaro outside the submitted work. D.M. O'Malley reports other from Yale University (institutional support for the trial) during the conduct of the study; personal fees and other from Genentech/Roche, AstraZeneca, Tesaro/GSK, Clovis, Immunogen, Abbvie, Janssen/ J&J, Regeneron, GOG Foundation, Agenus, Merck, Eisai, Tarveda, and Iovance (personal consulting and advisory fees and institutional support for clinical research); other from Array Biopharma, EMD Sereno, Ergomed, Cerulean, BMS (institutional support for clinical research), and Myriad (personal support for advisory board); and personal fees from Ambry (personal support for advisory board) outside the submitted work. F.J. Backes reports personal fees from Clovis Oncology, Eisai Inc, Merck, Genentech, AstraZeneca, GlaxoSmithKline, and Agenus (advisory board) and other from CEC Oncology (CME lectures) outside the submitted work. B. Edraki reports personal fees from AstraZeneca (speakers bureau), Abbvie (ad hoc advisory board), and Clovis Oncology (speakers bureau) outside the submitted work. W. Lowery reports other from AstraZeneca (speakers bureau) outside the submitted work. E. Ratner is an advisory board member for Tesaro, Genentech, and Zai Labs. D.-A. Silasi reports personal fees from Zai Lab outside the submitted work. A.D. Santin reports grants from Genentech/Roche during the conduct of the study; personal fees and other from Merck and Puma (advisory board); and grants from Immunomedics, R-Pharma, Boehinger-Ingelheim, Synthon, Merck, Gilead, Genentech/Roche, and Tesaro outside the submitted work. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
©2020 American Association for Cancer Research.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Purpose: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/ paclitaxel (C/P), is recognized as an alternative in treating advanced/ recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. Patients and Methods: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints. Results: Sixty-one patients were randomized. After a median-follow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28–0.76; P = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23–0.83; P = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03–0.48; P = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34–0.99; P = 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR = 0.49; 90% CI, 0.25–0.97; P = 0.041). Toxicity was not different between arms. Conclusions: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.
AB - Purpose: Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb targeting Her2/Neu, in combination with carboplatin/ paclitaxel (C/P), is recognized as an alternative in treating advanced/ recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. Patients and Methods: Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints. Results: Sixty-one patients were randomized. After a median-follow-up of 25.9 months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28–0.76; P = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23–0.83; P = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03–0.48; P = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34–0.99; P = 0.046). The benefit was most notable in those with stage III to IV disease, with survival median not reached in the T-arm versus 24.4 months in the control arm (HR = 0.49; 90% CI, 0.25–0.97; P = 0.041). Toxicity was not different between arms. Conclusions: Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III to IV disease.
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U2 - 10.1158/1078-0432.CCR-20-0953
DO - 10.1158/1078-0432.CCR-20-0953
M3 - Article
C2 - 32601075
AN - SCOPUS:85089128297
VL - 26
SP - 3928
EP - 3935
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 15
ER -