A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer

T. Ciuleanu, C. M. Tsai, C. J. Tsao, J. Milanowski, D. Amoroso, D. S. Heo, H. J M Groen, A. Szczesna, C. Y. Chung, T. Y. Chao, G. Middleton, A. Zeaiter, G. Klingelschmitt, B. Klughammer, N. Thatcher

Research output: Contribution to journalArticle

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Abstract

Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15. mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150. mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. Results: All randomized patients (n= 63 BE; n= 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p= 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.

Original languageEnglish
Pages (from-to)276-281
Number of pages6
JournalLung Cancer
Volume82
Issue number2
DOIs
Publication statusPublished - Nov 2013

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Non-Small Cell Lung Carcinoma
Disease-Free Survival
Drug Therapy
gemcitabine
Therapeutics
Disease Progression
Confidence Intervals
Safety
Carboplatin
Paclitaxel
Bevacizumab
Erlotinib Hydrochloride
Epidermal Growth Factor Receptor
Sample Size
Protein-Tyrosine Kinases
Cisplatin
Survival Rate
Incidence
Pharmaceutical Preparations

Keywords

  • Bevacizumab
  • Combination therapy
  • Erlotinib
  • First-line
  • Non-small cell lung cancer
  • Non-squamous

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer. / Ciuleanu, T.; Tsai, C. M.; Tsao, C. J.; Milanowski, J.; Amoroso, D.; Heo, D. S.; Groen, H. J M; Szczesna, A.; Chung, C. Y.; Chao, T. Y.; Middleton, G.; Zeaiter, A.; Klingelschmitt, G.; Klughammer, B.; Thatcher, N.

In: Lung Cancer, Vol. 82, No. 2, 11.2013, p. 276-281.

Research output: Contribution to journalArticle

Ciuleanu, T, Tsai, CM, Tsao, CJ, Milanowski, J, Amoroso, D, Heo, DS, Groen, HJM, Szczesna, A, Chung, CY, Chao, TY, Middleton, G, Zeaiter, A, Klingelschmitt, G, Klughammer, B & Thatcher, N 2013, 'A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer', Lung Cancer, vol. 82, no. 2, pp. 276-281. https://doi.org/10.1016/j.lungcan.2013.08.002
Ciuleanu, T. ; Tsai, C. M. ; Tsao, C. J. ; Milanowski, J. ; Amoroso, D. ; Heo, D. S. ; Groen, H. J M ; Szczesna, A. ; Chung, C. Y. ; Chao, T. Y. ; Middleton, G. ; Zeaiter, A. ; Klingelschmitt, G. ; Klughammer, B. ; Thatcher, N. / A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer. In: Lung Cancer. 2013 ; Vol. 82, No. 2. pp. 276-281.
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abstract = "Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15. mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150. mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. Results: All randomized patients (n= 63 BE; n= 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95{\%} confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95{\%} CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p= 0.0183). The incidence of death was 19{\%} for BE treatment compared with 11.5{\%} for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.",
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T1 - A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer

AU - Ciuleanu, T.

AU - Tsai, C. M.

AU - Tsao, C. J.

AU - Milanowski, J.

AU - Amoroso, D.

AU - Heo, D. S.

AU - Groen, H. J M

AU - Szczesna, A.

AU - Chung, C. Y.

AU - Chao, T. Y.

AU - Middleton, G.

AU - Zeaiter, A.

AU - Klingelschmitt, G.

AU - Klughammer, B.

AU - Thatcher, N.

PY - 2013/11

Y1 - 2013/11

N2 - Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15. mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150. mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. Results: All randomized patients (n= 63 BE; n= 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p= 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.

AB - Background: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. Methods: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15. mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150. mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. Results: All randomized patients (n= 63 BE; n= 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p= 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. Conclusions: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.

KW - Bevacizumab

KW - Combination therapy

KW - Erlotinib

KW - First-line

KW - Non-small cell lung cancer

KW - Non-squamous

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