Phase III Randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression

CALGB 30801 (Alliance)

Martin J. Edelman, Xiaofei Wang, Lydia Hodgson, Richard T. Cheney, Maria Q. Baggstrom, Sachdev P. Thomas, Ajeet Gajra, Erin Bertino, Karen L. Reckamp, Julian R Molina, Joan H. Schiller, Kisha Mitchell-Richards, Paula N. Friedman, Jon Ritter, Ginger Milne, Olwen M. Hahn, Thomas E. Stinchcombe, Everett E. Vokes

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression $ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index $ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index $ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 $ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.

Original languageEnglish (US)
Pages (from-to)2184-2192
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number19
DOIs
StatePublished - Jul 1 2017

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Celecoxib
Cyclooxygenase 2
Non-Small Cell Lung Carcinoma
Leukemia
Placebos
Drug Therapy
Neoplasms
Histology
Carboplatin
Immunohistochemistry
gemcitabine
Dinoprostone
Disease-Free Survival
Pemetrexed

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase III Randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression : CALGB 30801 (Alliance). / Edelman, Martin J.; Wang, Xiaofei; Hodgson, Lydia; Cheney, Richard T.; Baggstrom, Maria Q.; Thomas, Sachdev P.; Gajra, Ajeet; Bertino, Erin; Reckamp, Karen L.; Molina, Julian R; Schiller, Joan H.; Mitchell-Richards, Kisha; Friedman, Paula N.; Ritter, Jon; Milne, Ginger; Hahn, Olwen M.; Stinchcombe, Thomas E.; Vokes, Everett E.

In: Journal of Clinical Oncology, Vol. 35, No. 19, 01.07.2017, p. 2184-2192.

Research output: Contribution to journalArticle

Edelman, MJ, Wang, X, Hodgson, L, Cheney, RT, Baggstrom, MQ, Thomas, SP, Gajra, A, Bertino, E, Reckamp, KL, Molina, JR, Schiller, JH, Mitchell-Richards, K, Friedman, PN, Ritter, J, Milne, G, Hahn, OM, Stinchcombe, TE & Vokes, EE 2017, 'Phase III Randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression: CALGB 30801 (Alliance)', Journal of Clinical Oncology, vol. 35, no. 19, pp. 2184-2192. https://doi.org/10.1200/JCO.2016.71.3743
Edelman, Martin J. ; Wang, Xiaofei ; Hodgson, Lydia ; Cheney, Richard T. ; Baggstrom, Maria Q. ; Thomas, Sachdev P. ; Gajra, Ajeet ; Bertino, Erin ; Reckamp, Karen L. ; Molina, Julian R ; Schiller, Joan H. ; Mitchell-Richards, Kisha ; Friedman, Paula N. ; Ritter, Jon ; Milne, Ginger ; Hahn, Olwen M. ; Stinchcombe, Thomas E. ; Vokes, Everett E. / Phase III Randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression : CALGB 30801 (Alliance). In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 19. pp. 2184-2192.
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abstract = "Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression $ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index $ 4 with hazard ratio of 0.645 with approximately 85{\%} power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index $ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 $ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.",
author = "Edelman, {Martin J.} and Xiaofei Wang and Lydia Hodgson and Cheney, {Richard T.} and Baggstrom, {Maria Q.} and Thomas, {Sachdev P.} and Ajeet Gajra and Erin Bertino and Reckamp, {Karen L.} and Molina, {Julian R} and Schiller, {Joan H.} and Kisha Mitchell-Richards and Friedman, {Paula N.} and Jon Ritter and Ginger Milne and Hahn, {Olwen M.} and Stinchcombe, {Thomas E.} and Vokes, {Everett E.}",
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T1 - Phase III Randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression

T2 - CALGB 30801 (Alliance)

AU - Edelman, Martin J.

AU - Wang, Xiaofei

AU - Hodgson, Lydia

AU - Cheney, Richard T.

AU - Baggstrom, Maria Q.

AU - Thomas, Sachdev P.

AU - Gajra, Ajeet

AU - Bertino, Erin

AU - Reckamp, Karen L.

AU - Molina, Julian R

AU - Schiller, Joan H.

AU - Mitchell-Richards, Kisha

AU - Friedman, Paula N.

AU - Ritter, Jon

AU - Milne, Ginger

AU - Hahn, Olwen M.

AU - Stinchcombe, Thomas E.

AU - Vokes, Everett E.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression $ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index $ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index $ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 $ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.

AB - Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression $ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index $ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index $ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 $ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.

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