Jill Gilbert1, Michael J Schell2, Xiuhua Zhao3, Barbara Murphy4, Tawee Tanvetyanon5, Marino E Leon6, D Neil Hayes7, Missak Haigentz8, Nabil Saba9, Jorge Nieva10, Justin Bishop11, David Sidransky12, Rajani Ravi13, Atul Bedi14, Christine H Chung15. 1. Vanderbilt University, Nashville, TN, United States. Electronic address: jill.gilbert@vanderbilt.edu. 2. H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Michael.Schell@moffitt.org. 3. H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Xiuhua.Zhao@moffitt.org. 4. Vanderbilt University, Nashville, TN, United States. Electronic address: barbara.murphy@Vanderbilt.Edu. 5. H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Tawee.Tanvetyanon@moffitt.org. 6. H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Marino.Leon@Moffitt.org. 7. UNC Lineberger Cancer Center, Chapel Hill, NC, United States. Electronic address: hayes@med.unc.edu. 8. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, United States. Electronic address: mhaigent@montefiore.org. 9. Emory Winship Cancer Institute, Atlanta, GA, United States. Electronic address: NFSABA@emory.edu. 10. University of Southern California, Los Angeles, CA, United States. Electronic address: Jorge.Nieva@med.usc.edu. 11. Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: jbishop@jhmi.edu. 12. Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: dsidrans@jhmi.edu. 13. Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: ravira@jhmi.edu. 14. Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: abedi1@jhmi.edu. 15. Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: cchung11@jhmi.edu.
Abstract
INTRODUCTION: A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit. MATERIAL AND METHODS: In a randomized phase II study, R/M HNSCC patients were treated with cetuximab 400mg/m(2) IV on day 1 followed by 250mg/m(2) IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400mg PO twice-a-day (Arm B). Each cycle was 21days. Tumor p16 and HPV status, and plasma immunomodulatory cytokine levels were assessed. RESULTS: Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned treatments and 43 were evaluable for response. Overall response rate was 8% for both arms. Median overall survival (OS) and progression-free survival (PFS) were 9.0 and 3.0months in Arm A, and 5.7 and 3.2months in Arm B, respectively. Forty-four patients had tumors available for p16 staining (35-negative, 9-positive). Three of nine p16-positive tumors were also HPV positive. The p16-negative patients had significantly better PFS compared to the p16-positive patients (3.7 vs. 1.6months; p-value: 0.03), regardless of study arms. Twenty-four plasma samples were tested for 12 cytokine levels and patients with higher TGFβ1 levels had inferior PFS compared to lower levels (1.9 vs. 4.7months; adjusted p-value: 0.015), regardless of study arms. CONCLUSIONS: A subset of R/M patients with p16-negative tumors or lower plasma TGFβ1 levels had longer PFS given the cetuximab-based therapy. However, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit.
RCT Entities:
INTRODUCTION: A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit. MATERIAL AND METHODS: In a randomized phase II study, R/M HNSCC patients were treated with cetuximab 400mg/m(2) IV on day 1 followed by 250mg/m(2) IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400mg PO twice-a-day (Arm B). Each cycle was 21days. Tumorp16 and HPV status, and plasma immunomodulatory cytokine levels were assessed. RESULTS: Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned treatments and 43 were evaluable for response. Overall response rate was 8% for both arms. Median overall survival (OS) and progression-free survival (PFS) were 9.0 and 3.0months in Arm A, and 5.7 and 3.2months in Arm B, respectively. Forty-four patients had tumors available for p16 staining (35-negative, 9-positive). Three of nine p16-positive tumors were also HPV positive. The p16-negative patients had significantly better PFS compared to the p16-positive patients (3.7 vs. 1.6months; p-value: 0.03), regardless of study arms. Twenty-four plasma samples were tested for 12 cytokine levels and patients with higher TGFβ1 levels had inferior PFS compared to lower levels (1.9 vs. 4.7months; adjusted p-value: 0.015), regardless of study arms. CONCLUSIONS: A subset of R/M patients with p16-negative tumors or lower plasma TGFβ1 levels had longer PFS given the cetuximab-based therapy. However, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit.
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