DOI: 10.1200/jco.2005.02.840. TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non

TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer

10.1200/jco.2005.02.840

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

Purpose Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non–small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC. Patients and Methods TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response. Results There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P = .95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea). Conclusion Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials.

Bibliography

Herbst, R. S., Prager, D., Hermann, R., Fehrenbacher, L., Johnson, B. E., Sandler, A., Kris, M. G., Tran, H. T., Klein, P., Li, X., Ramies, D., Johnson, D. H., & Miller, V. A. (2005). TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced NonâSmall-Cell Lung Cancer. Journal of Clinical Oncology, 23(25), 5892â5899.

Authors 13

Roy S. Herbst (first)
Diane Prager (additional)
Robert Hermann (additional)
Lou Fehrenbacher (additional)
Bruce E. Johnson (additional)
Alan Sandler (additional)
Mark G. Kris (additional)
Hai T. Tran (additional)
Pam Klein (additional)
Xin Li (additional)
David Ramies (additional)
David H. Johnson (additional)
Vincent A. Miller (additional)

References 22 Referenced 1,152

Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000: The global picture. Eur J Cancer 37:S4,2001-S66, (suppl 8) (10.1016/S0959-8049(01)00267-2)
10.1158/1078-0432.CCR-040021
10.1200/JCO.2001.19.13.3267
10.1200/JCO.2004.06.075
10.1200/JCO.2004.11.057
10.1200/JCO.2004.08.163
10.1001/jama.290.16.2149
10.1097/01.cad.0000127664.66472.60
Declaration of Helsinki . Adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975, and the 35th World Medical Assembly, Venice, Italy, October, 1983
10.1056/NEJMoa011954
10.1200/JCO.2001.19.13.3210
10.1093/jnci/92.3.205
DakoCytomation PharmDx™ kit . Carpenteria, CA, DakoCytomation Inc, 2004
10.1126/science.1099314
10.1056/NEJMoa040938
Tran HT, Zinner R, Blumenschein GR, et al: Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial of paclitaxel (pac) and carboplatin (c) combined with erlotinib (e) or placebo in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 22:139,2004, (abstr 2050) (10.1200/jco.2004.22.90140.2050)
10.1200/JCO.2004.07.215
10.1200/jco.2004.22.14_suppl.567
10.1200/JCO.2002.06.140
10.1073/pnas.0405220101
Tracy S, Mukohara T, Hansen M, et al: Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res 68:7241,2004-7244, (10.1158/0008-5472.CAN-04-1905)
Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, et al: Chromosomal alterationsin lung adenocarcinoma from smokers and nonsmokers. Cancer Res 61:1309,2001-1313,

Dates

Type	When
Created	20 years, 1 month ago (July 25, 2005, 8:44 p.m.)
Deposited	3 years, 3 months ago (May 25, 2022, 5:18 p.m.)
Indexed	1 day, 10 hours ago (Sept. 3, 2025, 6:45 a.m.)
Issued	20 years ago (Sept. 1, 2005)
Published	20 years ago (Sept. 1, 2005)
Published Print	20 years ago (Sept. 1, 2005)

Funders 0

None

BibTeX

@article{Herbst_2005, title={TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer}, volume={23}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2005.02.840}, DOI={10.1200/jco.2005.02.840}, number={25}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={Herbst, Roy S. and Prager, Diane and Hermann, Robert and Fehrenbacher, Lou and Johnson, Bruce E. and Sandler, Alan and Kris, Mark G. and Tran, Hai T. and Klein, Pam and Li, Xin and Ramies, David and Johnson, David H. and Miller, Vincent A.}, year={2005}, month=sep, pages={5892–5899} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        3
      ]
    ],
    "date-time": "2025-09-03T10:45:19Z",
    "timestamp": 1756896319163
  },
  "reference-count": 22,
  "publisher": "American Society of Clinical Oncology (ASCO)",
  "issue": "25",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        9,
        1
      ]
    ]
  },
  "abstract": "<jats:sec><jats:title>Purpose</jats:title><jats:p> Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non\u2013small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P = .95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials. </jats:p></jats:sec>",
  "DOI": "10.1200/jco.2005.02.840",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        7,
        26
      ]
    ],
    "date-time": "2005-07-26T00:44:55Z",
    "timestamp": 1122338695000
  },
  "page": "5892-5899",
  "source": "Crossref",
  "is-referenced-by-count": 1152,
  "title": "TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non\u2013Small-Cell Lung Cancer",
  "prefix": "10.1200",
  "volume": "23",
  "author": [
    {
      "given": "Roy S.",
      "family": "Herbst",
      "sequence": "first",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Diane",
      "family": "Prager",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Robert",
      "family": "Hermann",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Lou",
      "family": "Fehrenbacher",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Bruce E.",
      "family": "Johnson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Alan",
      "family": "Sandler",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Mark G.",
      "family": "Kris",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Hai T.",
      "family": "Tran",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Pam",
      "family": "Klein",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Xin",
      "family": "Li",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "David",
      "family": "Ramies",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "David H.",
      "family": "Johnson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    },
    {
      "given": "Vincent A.",
      "family": "Miller",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group"
        }
      ]
    }
  ],
  "member": "233",
  "reference": [
    {
      "key": "R1",
      "doi-asserted-by": "crossref",
      "unstructured": "Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000: The global picture. Eur J Cancer 37:S4,2001-S66,  (suppl 8)",
      "DOI": "10.1016/S0959-8049(01)00267-2"
    },
    {
      "key": "R2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/1078-0432.CCR-040021"
    },
    {
      "key": "R3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2001.19.13.3267"
    },
    {
      "key": "R4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2004.06.075"
    },
    {
      "key": "R5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2004.11.057"
    },
    {
      "key": "R6",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2004.08.163"
    },
    {
      "key": "R7",
      "doi-asserted-by": "publisher",
      "DOI": "10.1001/jama.290.16.2149"
    },
    {
      "key": "R9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1097/01.cad.0000127664.66472.60"
    },
    {
      "key": "R10",
      "unstructured": "Declaration of Helsinki . Adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975, and the 35th World Medical Assembly, Venice, Italy, October, 1983"
    },
    {
      "key": "R11",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJMoa011954"
    },
    {
      "key": "R12",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2001.19.13.3210"
    },
    {
      "key": "R13",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnci/92.3.205"
    },
    {
      "key": "R14",
      "unstructured": "DakoCytomation PharmDx\u2122 kit . Carpenteria, CA, DakoCytomation Inc, 2004"
    },
    {
      "key": "R15",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1099314"
    },
    {
      "key": "R16",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJMoa040938"
    },
    {
      "key": "R17",
      "doi-asserted-by": "crossref",
      "unstructured": "Tran HT, Zinner R, Blumenschein GR, et al: Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial of paclitaxel (pac) and carboplatin (c) combined with erlotinib (e) or placebo in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 22:139,2004,  (abstr 2050)",
      "DOI": "10.1200/jco.2004.22.90140.2050"
    },
    {
      "key": "R18",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2004.07.215"
    },
    {
      "key": "R19",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/jco.2004.22.14_suppl.567"
    },
    {
      "key": "R20",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.2002.06.140"
    },
    {
      "key": "R21",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0405220101"
    },
    {
      "key": "R21A",
      "doi-asserted-by": "crossref",
      "unstructured": "Tracy S, Mukohara T, Hansen M, et al: Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res 68:7241,2004-7244,",
      "DOI": "10.1158/0008-5472.CAN-04-1905"
    },
    {
      "key": "R22",
      "unstructured": "Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, et al: Chromosomal alterationsin lung adenocarcinoma from smokers and nonsmokers. Cancer Res 61:1309,2001-1313,"
    }
  ],
  "container-title": "Journal of Clinical Oncology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2005.02.840",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        5,
        25
      ]
    ],
    "date-time": "2022-05-25T21:18:58Z",
    "timestamp": 1653513538000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://ascopubs.org/doi/10.1200/JCO.2005.02.840"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        9,
        1
      ]
    ]
  },
  "references-count": 22,
  "journal-issue": {
    "issue": "25",
    "published-print": {
      "date-parts": [
        [
          2005,
          9,
          1
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1200/JCO.2005.02.840"
  ],
  "URL": "http://dx.doi.org/10.1200/JCO.2005.02.840",
  "relation": {},
  "ISSN": [
    "0732-183X",
    "1527-7755"
  ],
  "subject": [],
  "container-title-short": "JCO",
  "published": {
    "date-parts": [
      [
        2005,
        9,
        1
      ]
    ]
  }
}