Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer

Roman Perez-Soler, Abraham Chachoua, Lisa A. Hammond, Eric K. Rowinsky, Mark Huberman, Daniel Karp, James Rigas, Gary M. Clark, Pedro Santabárbara, Philip Bonomi

Research output: Contribution to journalArticle

978 Citations (Scopus)

Abstract

Purpose: Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement. Patients and Methods: Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival. Results: The objective response rate was 12.3% (95% CI, 5.1% to 23.7%). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95% CI, 4.8 to 13.9 months), and the 1-year survival rate was 40% (95% CI, 28% to 54%). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75% and 56% of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash. Conclusion: Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.

Original languageEnglish (US)
Pages (from-to)3238-3247
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number16
DOIs
StatePublished - 2004
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Exanthema
Survival
Neoplasms
Quality of Life
Diarrhea
Drug Therapy
Platinum
Proportional Hazards Models
Epidermal Growth Factor Receptor
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Erlotinib Hydrochloride
Lung Neoplasms
Survival Rate
Biomarkers
Organizations
Staining and Labeling
Therapeutics
Research

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. / Perez-Soler, Roman; Chachoua, Abraham; Hammond, Lisa A.; Rowinsky, Eric K.; Huberman, Mark; Karp, Daniel; Rigas, James; Clark, Gary M.; Santabárbara, Pedro; Bonomi, Philip.

In: Journal of Clinical Oncology, Vol. 22, No. 16, 2004, p. 3238-3247.

Research output: Contribution to journalArticle

Perez-Soler, R, Chachoua, A, Hammond, LA, Rowinsky, EK, Huberman, M, Karp, D, Rigas, J, Clark, GM, Santabárbara, P & Bonomi, P 2004, 'Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer', Journal of Clinical Oncology, vol. 22, no. 16, pp. 3238-3247. https://doi.org/10.1200/JCO.2004.11.057
Perez-Soler, Roman ; Chachoua, Abraham ; Hammond, Lisa A. ; Rowinsky, Eric K. ; Huberman, Mark ; Karp, Daniel ; Rigas, James ; Clark, Gary M. ; Santabárbara, Pedro ; Bonomi, Philip. / Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 16. pp. 3238-3247.
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abstract = "Purpose: Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement. Patients and Methods: Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival. Results: The objective response rate was 12.3{\%} (95{\%} CI, 5.1{\%} to 23.7{\%}). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95{\%} CI, 4.8 to 13.9 months), and the 1-year survival rate was 40{\%} (95{\%} CI, 28{\%} to 54{\%}). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75{\%} and 56{\%} of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash. Conclusion: Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.",
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T1 - Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer

AU - Perez-Soler, Roman

AU - Chachoua, Abraham

AU - Hammond, Lisa A.

AU - Rowinsky, Eric K.

AU - Huberman, Mark

AU - Karp, Daniel

AU - Rigas, James

AU - Clark, Gary M.

AU - Santabárbara, Pedro

AU - Bonomi, Philip

PY - 2004

Y1 - 2004

N2 - Purpose: Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement. Patients and Methods: Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival. Results: The objective response rate was 12.3% (95% CI, 5.1% to 23.7%). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95% CI, 4.8 to 13.9 months), and the 1-year survival rate was 40% (95% CI, 28% to 54%). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75% and 56% of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash. Conclusion: Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.

AB - Purpose: Erlotinib is a highly specific epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. This phase II study of erlotinib in patients with HER1/EGFR-expressing non-small-cell lung cancer previously treated with platinum-based chemotherapy evaluated tumor response, survival, and symptom improvement. Patients and Methods: Fifty-seven patients received an oral, continuous daily dose of 150 mg of erlotinib. Assessments of objective response used WHO and Response Evaluation Criteria in Solid Tumors criteria. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, supplemented with a lung cancer module, Quality of Life Questionnaire LC13, was used to measure health-related quality of life. Additional analyses were performed to identify predictors of response and survival. Results: The objective response rate was 12.3% (95% CI, 5.1% to 23.7%). Responses were observed regardless of type or number of prior chemotherapy regimens. Median survival time was 8.4 months (95% CI, 4.8 to 13.9 months), and the 1-year survival rate was 40% (95% CI, 28% to 54%). Erlotinib therapy was associated with tumor-related symptom improvement. The drug was well tolerated; drug-related cutaneous rash and diarrhea were observed in 75% and 56% of patients, respectively. One patient experienced toxicity consisting of severe grade 3 rash and diarrhea. Time since diagnosis and good performance status were significant predictors of survival in a multivariate Cox proportional hazards model, whereas HER1/EGFR staining intensity was not. Additionally, survival correlated with the occurrence and severity of rash. Conclusion: Erlotinib was active and well tolerated in this patient population, and further clinical development is clearly warranted. Cutaneous rash seems to be a surrogate marker of clinical benefit, but this finding should be confirmed in ongoing and future studies.

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