Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer

Joseph M. Herman, Katherine Y. Fan, Aaron T. Wild, Amy Hacker-Prietz, Laura D. Wood, Amanda L. Blackford, Susannah Ellsworth, Lei Zheng, Dung T. Le, Ana De Jesus-Acosta, Manuel Hidalgo, Ross C. Donehower, Richard D. Schulick, Barish H. Edil, Michael A. Choti, Ralph H. Hruban, Timothy M. Pawlik, John L. Cameron, Daniel A. Laheru, Christopher L. Wolfgang

Research output: Contribution to journalArticle

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Abstract

Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine- erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number4
DOIs
StatePublished - Jul 15 2013

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chemotherapy
Adjuvant Chemotherapy
Pancreatic Neoplasms
cancer
Survival
gemcitabine
Adenocarcinoma
Recurrence
Radiotherapy
radiation therapy
confidence
therapy
Confidence Intervals
dermatitis
Drug Therapy
Radiation Oncology
intervals
Erlotinib Hydrochloride
Dermatitis
lymphatic system

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer. / Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; Pawlik, Timothy M.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.

In: International Journal of Radiation Oncology Biology Physics, Vol. 86, No. 4, 15.07.2013, p. 678-685.

Research output: Contribution to journalArticle

Herman, JM, Fan, KY, Wild, AT, Hacker-Prietz, A, Wood, LD, Blackford, AL, Ellsworth, S, Zheng, L, Le, DT, De Jesus-Acosta, A, Hidalgo, M, Donehower, RC, Schulick, RD, Edil, BH, Choti, MA, Hruban, RH, Pawlik, TM, Cameron, JL, Laheru, DA & Wolfgang, CL 2013, 'Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer', International Journal of Radiation Oncology Biology Physics, vol. 86, no. 4, pp. 678-685. https://doi.org/10.1016/j.ijrobp.2013.03.032
Herman, Joseph M. ; Fan, Katherine Y. ; Wild, Aaron T. ; Hacker-Prietz, Amy ; Wood, Laura D. ; Blackford, Amanda L. ; Ellsworth, Susannah ; Zheng, Lei ; Le, Dung T. ; De Jesus-Acosta, Ana ; Hidalgo, Manuel ; Donehower, Ross C. ; Schulick, Richard D. ; Edil, Barish H. ; Choti, Michael A. ; Hruban, Ralph H. ; Pawlik, Timothy M. ; Cameron, John L. ; Laheru, Daniel A. ; Wolfgang, Christopher L. / Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 86, No. 4. pp. 678-685.
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abstract = "Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20{\%} for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine- erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85{\%} of patients, and margins were positive in 17{\%}. The median RFS was 15.6 months (95{\%} confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95{\%} CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31{\%}/2{\%} and 35{\%}/8{\%}, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.",
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T1 - Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer

AU - Herman, Joseph M.

AU - Fan, Katherine Y.

AU - Wild, Aaron T.

AU - Hacker-Prietz, Amy

AU - Wood, Laura D.

AU - Blackford, Amanda L.

AU - Ellsworth, Susannah

AU - Zheng, Lei

AU - Le, Dung T.

AU - De Jesus-Acosta, Ana

AU - Hidalgo, Manuel

AU - Donehower, Ross C.

AU - Schulick, Richard D.

AU - Edil, Barish H.

AU - Choti, Michael A.

AU - Hruban, Ralph H.

AU - Pawlik, Timothy M.

AU - Cameron, John L.

AU - Laheru, Daniel A.

AU - Wolfgang, Christopher L.

PY - 2013/7/15

Y1 - 2013/7/15

N2 - Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine- erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

AB - Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine- erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

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