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

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25 Scopus citations

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

ASJC Scopus subject areas

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

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    Herman, J. M., Fan, K. Y., Wild, A. T., Hacker-Prietz, A., Wood, L. D., Blackford, A. L., Ellsworth, S., Zheng, L., Le, D. T., De Jesus-Acosta, A., Hidalgo, M., Donehower, R. C., Schulick, R. D., Edil, B. H., Choti, M. A., Hruban, R. H., Pawlik, T. M., Cameron, J. L., Laheru, D. A., & Wolfgang, C. L. (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, 86(4), 678-685. https://doi.org/10.1016/j.ijrobp.2013.03.032