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

Jill Gilbert, Michael J. Schell, Xiuhua Zhao, Barbara Murphy, Tawee Tanvetyanon, Marino E. Leon, D. Neil Hayes, Missak Haigentz, Nabil Saba, Jorge Nieva, Justin Bishop, David Sidransky, Rajani Ravi, Atul Bedi, Christine H. Chung

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 400 mg/m2IV on day 1 followed by 250 mg/m2IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400 mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p1 6 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 3.0 months in Arm A, and 5.7 and 3.2 months 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. 1.6 months; 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. 4.7 months; 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.

Original languageEnglish (US)
Pages (from-to)376-382
Number of pages7
JournalOral Oncology
Volume51
Issue number4
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Disease-Free Survival
Neoplasms
Cytokines
Human papillomavirus 6
sorafenib
Cetuximab
Carcinoma, squamous cell of head and neck
Negative Staining
Appointments and Schedules
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

Gilbert, Jill ; Schell, Michael J. ; Zhao, Xiuhua ; Murphy, Barbara ; Tanvetyanon, Tawee ; Leon, Marino E. ; Hayes, D. Neil ; Haigentz, Missak ; Saba, Nabil ; Nieva, Jorge ; Bishop, Justin ; Sidransky, David ; Ravi, Rajani ; Bedi, Atul ; Chung, Christine H. / 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. In: Oral Oncology. 2015 ; Vol. 51, No. 4. pp. 376-382.
@article{078a2a37c12f480bbbd63f57bbecd198,
title = "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",
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 400 mg/m2IV on day 1 followed by 250 mg/m2IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400 mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p1 6 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 3.0 months in Arm A, and 5.7 and 3.2 months 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. 1.6 months; 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. 4.7 months; 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.",
author = "Jill Gilbert and Schell, {Michael J.} and Xiuhua Zhao and Barbara Murphy and Tawee Tanvetyanon and Leon, {Marino E.} and Hayes, {D. Neil} and Missak Haigentz and Nabil Saba and Jorge Nieva and Justin Bishop and David Sidransky and Rajani Ravi and Atul Bedi and Chung, {Christine H.}",
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Gilbert, J, Schell, MJ, Zhao, X, Murphy, B, Tanvetyanon, T, Leon, ME, Hayes, DN, Haigentz, M, Saba, N, Nieva, J, Bishop, J, Sidransky, D, Ravi, R, Bedi, A & Chung, CH 2015, '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', Oral Oncology, vol. 51, no. 4, pp. 376-382. https://doi.org/10.1016/j.oraloncology.2014.12.011

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, Jill; Schell, Michael J.; Zhao, Xiuhua; Murphy, Barbara; Tanvetyanon, Tawee; Leon, Marino E.; Hayes, D. Neil; Haigentz, Missak; Saba, Nabil; Nieva, Jorge; Bishop, Justin; Sidransky, David; Ravi, Rajani; Bedi, Atul; Chung, Christine H.

In: Oral Oncology, Vol. 51, No. 4, 01.01.2015, p. 376-382.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Gilbert, Jill

AU - Schell, Michael J.

AU - Zhao, Xiuhua

AU - Murphy, Barbara

AU - Tanvetyanon, Tawee

AU - Leon, Marino E.

AU - Hayes, D. Neil

AU - Haigentz, Missak

AU - Saba, Nabil

AU - Nieva, Jorge

AU - Bishop, Justin

AU - Sidransky, David

AU - Ravi, Rajani

AU - Bedi, Atul

AU - Chung, Christine H.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 400 mg/m2IV on day 1 followed by 250 mg/m2IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400 mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p1 6 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 3.0 months in Arm A, and 5.7 and 3.2 months 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. 1.6 months; 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. 4.7 months; 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.

AB - 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 400 mg/m2IV on day 1 followed by 250 mg/m2IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400 mg PO twice-a-day (Arm B). Each cycle was 21 days. Tumor p1 6 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 3.0 months in Arm A, and 5.7 and 3.2 months 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. 1.6 months; 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. 4.7 months; 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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DO - 10.1016/j.oraloncology.2014.12.011

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JO - Oral Oncology

JF - Oral Oncology

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