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

G. 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, Lee 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, 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

Research output: Contribution to journalArticle

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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 - Jan 1 2011

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Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Pharmacokinetics
Survival
imetelstat
Bevacizumab
Disease Progression
Confidence Intervals
Drug Therapy
Incidence

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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

In: Annals of Oncology, Vol. 22, No. 9, 01.01.2011, p. 2057-2067.

Research output: Contribution to journalArticle

Blumenschein, GR, Kabbinavar, F, Menon, H, Mok, TSK, Stephenson, J, Beck, JT, Lakshmaiah, K, Reckamp, K, Hei, YJ, Kracht, K, Sun, YN, Sikorski, R, Schwartzberg, L, Au, AK, Cheng, CK, Mok, TSK, Tung, Y, Behera, D, Chacko, R, Lakshmaiah, K, Menon, H, Nirni, S, Pathak, A, Thirumulai, R, Arena, F, Beck, JT, Belman, N, Boccia, R, Chan, D, Clowney, B, Davidson, S, Del Prete, S, Dudek, A, Fain, J, Hagenstad, C, Henry, D, Hoang, T, Holladay, C, Hu, E, Kabbinavar, F, Kaywin, P, MacLaughlin, W, March, R, Marsland, T, Meza, L, Mott, F, Page, R, Paschold, E, Patel, G, Patel, R, Prow, D, Reckamp, K, Rosen, P, Sabbath, K, Samuels, B, Schwartzberg, L, Shah, M, Shtivelband, M, Singh, J, Stephenson, J, Subramaniam, D, Swanson, P, Thomas, M & Webb, R 2011, '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', Annals of Oncology, vol. 22, no. 9, pp. 2057-2067. https://doi.org/10.1093/annonc/mdq731
Blumenschein, G. R. ; Kabbinavar, F. ; Menon, H. ; Mok, T. S.K. ; Stephenson, J. ; Beck, J. T. ; Lakshmaiah, K. ; Reckamp, K. ; Hei, Y. J. ; Kracht, K. ; Sun, Y. N. ; Sikorski, R. ; Schwartzberg, Lee ; Au, A. K. ; Cheng, C. K. ; Mok, T. S.K. ; Tung, Y. ; Behera, D. ; Chacko, R. ; Lakshmaiah, K. ; Menon, H. ; Nirni, S. ; Pathak, A. ; Thirumulai, R. ; Arena, F. ; Beck, J. T. ; Belman, N. ; Boccia, R. ; Chan, D. ; Clowney, B. ; Davidson, S. ; Del Prete, S. ; Dudek, A. ; Fain, J. ; Hagenstad, C. ; Henry, D. ; Hoang, T. ; Holladay, C. ; Hu, E. ; Kabbinavar, F. ; Kaywin, P. ; MacLaughlin, W. ; March, R. ; Marsland, T. ; Meza, L. ; Mott, F. ; Page, R. ; Paschold, E. ; Patel, G. ; Patel, R. ; Prow, D. ; Reckamp, K. ; Rosen, P. ; Sabbath, K. ; Samuels, B. ; Schwartzberg, L. ; Shah, M. ; Shtivelband, M. ; Singh, J. ; Stephenson, J. ; Subramaniam, D. ; Swanson, P. ; Thomas, M. ; Webb, R. / 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. In: Annals of Oncology. 2011 ; Vol. 22, No. 9. pp. 2057-2067.
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title = "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",
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.",
author = "Blumenschein, {G. R.} and F. Kabbinavar and H. Menon and Mok, {T. S.K.} and J. Stephenson and Beck, {J. T.} and K. Lakshmaiah and K. Reckamp and Hei, {Y. J.} and K. Kracht and Sun, {Y. N.} and R. Sikorski and Lee Schwartzberg and Au, {A. K.} and Cheng, {C. K.} and Mok, {T. S.K.} and Y. Tung and D. Behera and R. Chacko and K. Lakshmaiah and H. Menon and S. Nirni and A. Pathak and R. Thirumulai and F. Arena and Beck, {J. T.} and N. Belman and R. Boccia and D. Chan and B. Clowney and S. Davidson and {Del Prete}, S. and A. Dudek and J. Fain and C. Hagenstad and D. Henry and T. Hoang and C. Holladay and E. Hu and F. Kabbinavar and P. Kaywin and W. MacLaughlin and R. March and T. Marsland and L. Meza and F. Mott and R. Page and E. Paschold and G. Patel and R. Patel and D. Prow and K. Reckamp and P. Rosen and K. Sabbath and B. Samuels and L. Schwartzberg and M. Shah and M. Shtivelband and J. Singh and J. Stephenson and D. Subramaniam and P. Swanson and M. Thomas and R. Webb",
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month = "1",
day = "1",
doi = "10.1093/annonc/mdq731",
language = "English (US)",
volume = "22",
pages = "2057--2067",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
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TY - JOUR

T1 - 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

AU - Blumenschein, G. R.

AU - Kabbinavar, F.

AU - Menon, H.

AU - Mok, T. S.K.

AU - Stephenson, J.

AU - Beck, J. T.

AU - Lakshmaiah, K.

AU - Reckamp, K.

AU - Hei, Y. J.

AU - Kracht, K.

AU - Sun, Y. N.

AU - Sikorski, R.

AU - Schwartzberg, Lee

AU - Au, A. K.

AU - Cheng, C. K.

AU - Mok, T. S.K.

AU - Tung, Y.

AU - Behera, D.

AU - Chacko, R.

AU - Lakshmaiah, K.

AU - Menon, H.

AU - Nirni, S.

AU - Pathak, A.

AU - Thirumulai, R.

AU - Arena, F.

AU - Beck, J. T.

AU - Belman, N.

AU - Boccia, R.

AU - Chan, D.

AU - Clowney, B.

AU - Davidson, S.

AU - Del Prete, S.

AU - Dudek, A.

AU - Fain, J.

AU - Hagenstad, C.

AU - Henry, D.

AU - Hoang, T.

AU - Holladay, C.

AU - Hu, E.

AU - Kabbinavar, F.

AU - Kaywin, P.

AU - MacLaughlin, W.

AU - March, R.

AU - Marsland, T.

AU - Meza, L.

AU - Mott, F.

AU - Page, R.

AU - Paschold, E.

AU - Patel, G.

AU - Patel, R.

AU - Prow, D.

AU - Reckamp, K.

AU - Rosen, P.

AU - Sabbath, K.

AU - Samuels, B.

AU - Schwartzberg, L.

AU - Shah, M.

AU - Shtivelband, M.

AU - Singh, J.

AU - Stephenson, J.

AU - Subramaniam, D.

AU - Swanson, P.

AU - Thomas, M.

AU - Webb, R.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

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JO - Annals of Oncology

JF - Annals of Oncology

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