Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma

Southwest oncology group-directed intergroup trial S0205

Philip A. Philip, Jacqueline Benedetti, Christopher L. Corless, Ralph Wong, Eileen M. O'Reilly, Patrick J. Flynn, Kendrith M. Rowland, James N. Atkins, Barry C. Mirtsching, Saul E. Rivkin, Alok A. Khorana, Bryan Goldman, Cecilia M. Fenoglio-Preiser, James L. Abbruzzese, Charles D. Blanke

Research output: Contribution to journalArticle

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Abstract

Purpose: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. Conclusion: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

Original languageEnglish (US)
Pages (from-to)3605-3610
Number of pages6
JournalJournal of Clinical Oncology
Volume28
Issue number22
DOIs
StatePublished - Aug 1 2010

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gemcitabine
Adenocarcinoma
Epidermal Growth Factor Receptor
Pancreatic Neoplasms
Treatment Failure
Disease-Free Survival
Pyridinolcarbamate
Monoclonal Antibodies
Cetuximab
Survival
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma : Southwest oncology group-directed intergroup trial S0205. / Philip, Philip A.; Benedetti, Jacqueline; Corless, Christopher L.; Wong, Ralph; O'Reilly, Eileen M.; Flynn, Patrick J.; Rowland, Kendrith M.; Atkins, James N.; Mirtsching, Barry C.; Rivkin, Saul E.; Khorana, Alok A.; Goldman, Bryan; Fenoglio-Preiser, Cecilia M.; Abbruzzese, James L.; Blanke, Charles D.

In: Journal of Clinical Oncology, Vol. 28, No. 22, 01.08.2010, p. 3605-3610.

Research output: Contribution to journalArticle

Philip, PA, Benedetti, J, Corless, CL, Wong, R, O'Reilly, EM, Flynn, PJ, Rowland, KM, Atkins, JN, Mirtsching, BC, Rivkin, SE, Khorana, AA, Goldman, B, Fenoglio-Preiser, CM, Abbruzzese, JL & Blanke, CD 2010, 'Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest oncology group-directed intergroup trial S0205', Journal of Clinical Oncology, vol. 28, no. 22, pp. 3605-3610. https://doi.org/10.1200/JCO.2009.25.7550
Philip, Philip A. ; Benedetti, Jacqueline ; Corless, Christopher L. ; Wong, Ralph ; O'Reilly, Eileen M. ; Flynn, Patrick J. ; Rowland, Kendrith M. ; Atkins, James N. ; Mirtsching, Barry C. ; Rivkin, Saul E. ; Khorana, Alok A. ; Goldman, Bryan ; Fenoglio-Preiser, Cecilia M. ; Abbruzzese, James L. ; Blanke, Charles D. / Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma : Southwest oncology group-directed intergroup trial S0205. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 22. pp. 3605-3610.
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abstract = "Purpose: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95{\%} CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90{\%} were positive, with no treatment benefit detected in this patient subset. Conclusion: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.",
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AU - Benedetti, Jacqueline

AU - Corless, Christopher L.

AU - Wong, Ralph

AU - O'Reilly, Eileen M.

AU - Flynn, Patrick J.

AU - Rowland, Kendrith M.

AU - Atkins, James N.

AU - Mirtsching, Barry C.

AU - Rivkin, Saul E.

AU - Khorana, Alok A.

AU - Goldman, Bryan

AU - Fenoglio-Preiser, Cecilia M.

AU - Abbruzzese, James L.

AU - Blanke, Charles D.

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N2 - Purpose: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. Patients and Methods: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. Results: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. Conclusion: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.

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