Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

Tanguy Y. Seiwert*, James M. Melotek, Elizabeth A. Blair, Kerstin M. Stenson, Joseph K. Salama, Mary Ellyn Witt, Ryan J. Brisson, Apoorva Chawla, Allison Dekker, Mark W. Lingen, Masha Kocherginsky, Victoria M. Villaflor, Ezra E W Cohen, Daniel J. Haraf, Everett E. Vokes

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume96
Issue number1
DOIs
StatePublished - Sep 1 2016

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Induction Chemotherapy
chemotherapy
Head and Neck Neoplasms
induction
Disease-Free Survival
cancer
progressions
Squamous Cell Neoplasms
Survival
Head
Arm
Radiotherapy
radiation therapy
grade
Hydroxyurea
Carboplatin
Paclitaxel
Cetuximab
Exanthema
Neutropenia

ASJC Scopus subject areas

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

Cite this

Seiwert, Tanguy Y. ; Melotek, James M. ; Blair, Elizabeth A. ; Stenson, Kerstin M. ; Salama, Joseph K. ; Witt, Mary Ellyn ; Brisson, Ryan J. ; Chawla, Apoorva ; Dekker, Allison ; Lingen, Mark W. ; Kocherginsky, Masha ; Villaflor, Victoria M. ; Cohen, Ezra E W ; Haraf, Daniel J. ; Vokes, Everett E. / Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer. In: International Journal of Radiation Oncology Biology Physics. 2016 ; Vol. 96, No. 1. pp. 21-29.
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title = "Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer",
abstract = "Purpose The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70{\%}. Results 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91{\%}. Severe toxicity on IC was limited to rash (23{\%} grade ≥3) and myelosuppression (38{\%} grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5{\%}) and Cetux-PX (84.9{\%}) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2{\%} for Cetux-FHX and 94.3{\%} for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1{\%}, 80.3{\%}, 15.7{\%}, and 7.4{\%}, respectively. The 5-year PFS and OS were 84.4{\%} and 91.3{\%}, respectively, among human papillomavirus (HPV)-positive patients and 65.9{\%} and 72.5{\%}, respectively, among HPV-negative patients. Conclusions The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.",
author = "Seiwert, {Tanguy Y.} and Melotek, {James M.} and Blair, {Elizabeth A.} and Stenson, {Kerstin M.} and Salama, {Joseph K.} and Witt, {Mary Ellyn} and Brisson, {Ryan J.} and Apoorva Chawla and Allison Dekker and Lingen, {Mark W.} and Masha Kocherginsky and Villaflor, {Victoria M.} and Cohen, {Ezra E W} and Haraf, {Daniel J.} and Vokes, {Everett E.}",
year = "2016",
month = "9",
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doi = "10.1016/j.ijrobp.2016.04.030",
language = "English (US)",
volume = "96",
pages = "21--29",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
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Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer. / Seiwert, Tanguy Y.; Melotek, James M.; Blair, Elizabeth A.; Stenson, Kerstin M.; Salama, Joseph K.; Witt, Mary Ellyn; Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison; Lingen, Mark W.; Kocherginsky, Masha; Villaflor, Victoria M.; Cohen, Ezra E W; Haraf, Daniel J.; Vokes, Everett E.

In: International Journal of Radiation Oncology Biology Physics, Vol. 96, No. 1, 01.09.2016, p. 21-29.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

AU - Seiwert, Tanguy Y.

AU - Melotek, James M.

AU - Blair, Elizabeth A.

AU - Stenson, Kerstin M.

AU - Salama, Joseph K.

AU - Witt, Mary Ellyn

AU - Brisson, Ryan J.

AU - Chawla, Apoorva

AU - Dekker, Allison

AU - Lingen, Mark W.

AU - Kocherginsky, Masha

AU - Villaflor, Victoria M.

AU - Cohen, Ezra E W

AU - Haraf, Daniel J.

AU - Vokes, Everett E.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Purpose The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.

AB - Purpose The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.

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