A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer

Jr R. Blumenschein, F. Kabbinavar, H. Menon, T. S K Mok, J. Stephenson, J. T. Beck, K. Lakshmaiah, K. Reckamp, Y. J. Hei, K. Kracht, Y. N. Sun, R. Sikorski, L. Schwartzberg, A. K. Au, C. K. Cheng, T. S K Mok, Y. Tung, D. Behera, R. Chacko, K. LakshmaiahH. Menon, S. Nirni, A. Pathak, R. Thirumulai, F. Arena, J. T. Beck, N. Belman, G. R. Blumenschein, R. Boccia, D. Chan, B. Clowney, S. Davidson, S. Del Prete, A. Dudek, J. Fain, C. Hagenstad, D. Henry, T. Hoang, C. Holladay, E. Hu, F. Kabbinavar, P. Kaywin, W. MacLaughlin, R. March, T. Marsland, L. Meza, F. Mott, R. Page, E. Paschold, G. Patel, R. Patel, D. Prow, K. Reckamp, P. Rosen, K. Sabbath, B. Samuels, L. Schwartzberg, M. Shah, M. Shtivelband, J. Singh, J. Stephenson, D. Subramaniam, P. Swanson, M. Thomas, R. Webb

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70 Scopus citations

Abstract

Background: This phase II study estimated the difference in objective response rate (ORR) among patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) receiving paclitaxel-carboplatin (CP) plus motesanib or bevacizumab. Patients and methods: Chemotherapy-naive patients (N = 186) were randomized 1:1:1 to receive CP plus motesanib 125 mg once daily (qd) (arm A), motesanib 75 mg twice daily (b.i.d.) 5 days on/2 days off (arm B), or bevacizumab 15 mg/kg every 3 weeks (q3w) (arm C). The primary end point was ORR (per RECIST). Other end points included progression-free survival (PFS), overall survival (OS), motesanib pharmacokinetics, and adverse events (AEs). Results: ORRs in the three arms were as follows: arm A, 30% (95% confidence interval 18% to 43%); arm B, 23% (13% to 36%); and arm C, 37% (25% to 50%). Median PFS in arm A was 7.7 months, arm B 5.8 months, and arm C 8.3 months; median OS for arm A was 14.0 months, arm B 12.8 months, and arm C 14.0 months. Incidence of AEs was greater in arms A and B than in arm C. More grade 5 AEs not attributable to disease progression occurred in arm B (n = 10) than in arms A (n = 4) and C (n = 4). Motesanib plasma Cmaxand Cminvalues were consistent with its pharmacokinetic properties observed in previous studies. Conclusions: The efficacy of 125 mg qd motesanib or bevacizumab plus CP was estimated to be comparable. Toxicity was higher but manageable in both motesanib arms. Efficacy and tolerability of motesanib 125 mg qd plus CP in advanced nonsquamous NSCLC are being further investigated in a phase III study.

Original languageEnglish (US)
Pages (from-to)2057-2067
Number of pages11
JournalAnnals of Oncology
Volume22
Issue number9
DOIs
StatePublished - Sep 2011

Bibliographical note

Funding Information:
G.R.B. has served as a consultant for and has received research funding from Amgen Inc.; T.S.K.M. has served as a consultant for Roche, AstraZeneca, and Eli Lily and has received honoraria from Roche, AstraZeneca, and Pfizer; J.S. has received funding from Amgen Inc.; J.T.B. has received research funding from Amgen Inc. and Genentech; K.R. has served as a consultant for Amgen Inc.; L.S. has served as a consultant and received honoraria from Amgen Inc.; F.K., K.L., and H.M. have no conflicts to disclose. Y.-J.H., K.K., Y.-N.S., and R.S. are employees of and stockholders in Amgen Inc.

Funding Information:
The following investigators participated in the study?Hong Kong SAR: A. K. Au, C. K. Cheng, T. S. K. Mok, Y. Tung; India: D. Behera, R. Chacko, K. Lakshmaiah, H. Menon, S. Nirni, A. Pathak, R. Thirumulai; United States: F. Arena, J. T. Beck, N. Belman, G. R. Blumenschein, R. Boccia, D. Chan, B. Clowney, S. Davidson, S. Del Prete, A. Dudek, J. Fain, C. Hagenstad, D. Henry, T. Hoang, C. Holladay, E. Hu, F. Kabbinavar, P. Kaywin, W. MacLaughlin, R. March, T. Marsland, L. Meza, F. Mott, R. Page, E. Paschold, G. Patel, R. Patel, D. Prow, K. Reckamp, P. Rosen, K. Sabbath, B. Samuels, L. Schwartzberg, M. Shah, M. Shtivelband, J. Singh, J. Stephenson, D. Subramaniam, P. Swanson, M. Thomas, and R. Webb. The authors acknowledge Ali Hassan (Complete Healthcare Communications Inc.), whose work was funded by Amgen Inc. and Beate D. Quednau (Amgen Inc.) for their assistance in the preparation of the manuscript; Cindy Wake and Bernd Bruenner (Amgen Inc.) for pharmacokinetic sample analysis; and Rebeca Melara (Amgen Inc.) for pharmacokinetic data analysis. The results of this study were presented in part at the 13th World Conference on Lung Cancer, 31 July to 2 August 2009, San Francisco, CA; at the Joint European Cancer Organization 15?34th European Society of Medical Oncology Multidisciplinary Congress, 20?24 September 2009, Berlin, Germany; and at the 46th Annual Meeting of the American Society of Clinical Oncology, 4?8 June 2010, Chicago, IL. Clinical Trial Registration: http://ClinicalTrials.gov; registration number: NCT00369070. Amgen Inc.; Millenium/Takeda. G.R.B. has served as a consultant for and has received research funding from Amgen Inc.; T.S.K.M. has served as a consultant for Roche, AstraZeneca, and Eli Lily and has received honoraria from Roche, AstraZeneca, and Pfizer; J.S. has received funding from Amgen Inc.; J.T.B. has received research funding from Amgen Inc. and Genentech; K.R. has served as a consultant for Amgen Inc.; L.S. has served as a consultant and received honoraria from Amgen Inc.; F.K. K.L. and H.M. have no conflicts to disclose. Y.-J.H. K.K. Y.-N.S. and R.S. are employees of and stockholders in Amgen Inc.

Funding Information:
The following investigators participated in the study—Hong Kong SAR: A. K. Au, C. K. Cheng, T. S. K. Mok, Y. Tung; India: D. Behera, R. Chacko, K. Lakshmaiah, H. Menon, S. Nirni, A. Pathak, R. Thirumulai; United States: F. Arena, J. T. Beck, N. Belman, G. R. Blumenschein, R. Boccia, D. Chan, B. Clowney, S. Davidson, S. Del Prete, A. Dudek, J. Fain, C. Hagenstad, D. Henry, T. Hoang, C. Holladay, E. Hu, F. Kabbinavar, P. Kaywin, W. MacLaughlin, R. March, T. Marsland, L. Meza, F. Mott, R. Page, E. Paschold, G. Patel, R. Patel, D. Prow, K. Reckamp, P. Rosen, K. Sabbath, B. Samuels, L. Schwartzberg, M. Shah, M. Shtivelband, J. Singh, J. Stephenson, D. Subramaniam, P. Swanson, M. Thomas, and R. Webb. The authors acknowledge Ali Hassan (Complete Healthcare Communications Inc.), whose work was funded by Amgen Inc., and Beate D. Quednau (Amgen Inc.) for their assistance in the preparation of the manuscript; Cindy Wake and Bernd Bruenner (Amgen Inc.) for pharmacokinetic sample analysis; and Rebeca Melara (Amgen Inc.) for pharmacokinetic data analysis. The results of this study were presented in part at the 13th World Conference on Lung Cancer, 31 July to 2 August 2009, San Francisco, CA; at the Joint European Cancer Organization 15–34th European Society of Medical Oncology Multidisciplinary Congress, 20–24 September 2009, Berlin, Germany; and at the 46th Annual Meeting of the American Society of Clinical Oncology, 4–8 June 2010, Chicago, IL. Clinical Trial Registration: http://ClinicalTrials.gov ; registration number: NCT00369070.

Keywords

  • Bevacizumab
  • Motesanib
  • Nonsquamous non-small-cell lung cancer
  • Objective response rate
  • Pharmacokinetics

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