A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma.

Gilbert J, Schell MJ, Zhao X, Murphy B, Tanvetyanon T, Leon ME, Neil Hayes D, Haigentz M, Saba N, Nieva J, Bishop J, Sidransky D, Ravi R, Bedi A, Chung CH
Oral Oncol. 2015 51 (4): 376-82

PMID: 25593015 · PMCID: PMC4459134 · DOI:10.1016/j.oraloncology.2014.12.011

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.

Copyright © 2014 Elsevier Ltd. All rights reserved.

MeSH Terms (15)

Adult Aged Antineoplastic Agents Carcinoma, Squamous Cell Cetuximab Female Head and Neck Neoplasms Humans Male Middle Aged Neoplasm Metastasis Niacinamide Phenylurea Compounds Recurrence Sorafenib

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