Tanguy Y Seiwert1, James M Melotek2, Elizabeth A Blair3, Kerstin M Stenson4, Joseph K Salama5, Mary Ellyn Witt2, Ryan J Brisson6, Apoorva Chawla6, Allison Dekker6, Mark W Lingen7, Masha Kocherginsky8, Victoria M Villaflor6, Ezra E W Cohen9, Daniel J Haraf2, Everett E Vokes6. 1. Departments of Medicine, University of Chicago, Chicago, Illinois. Electronic address: tseiwert@medicine.bsd.uchicago.edu. 2. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois. 3. Department of Otolaryngology, University of Chicago, Chicago, Illinois. 4. Department of Otolaryngology, Rush University, Chicago, Illinois. 5. Department of Radiation Oncology, Duke University, Durham, North Carolina. 6. Departments of Medicine, University of Chicago, Chicago, Illinois. 7. Department of Pathology, University of Chicago, Chicago, Illinois. 8. Department of Public Health Sciences, University of Chicago, Chicago, Illinois. 9. Moores Cancer Center, University of California, San Diego, San Diego, California.
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.
RCT Entities:
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.
Authors: J Martínez-Trufero; A Lozano Borbalas; I Pajares Bernad; M Taberna Sanz; E Ortega Izquierdo; B Cirauqui Cirauqui; J Rubió-Casadevall; M Plana Serrahima; J M Ponce Ortega; I Planas Toledano; J Caballero; J Marruecos Querol; L Iglesias Docampo; J Lambea Sorrosal; J C Adansa; R Mesía Nin Journal: Clin Transl Oncol Date: 2021-04-19 Impact factor: 3.405
Authors: Michael T Spiotto; Gina Jefferson; Barry Wenig; Michael Markiewicz; Ralph R Weichselbaum; Matthew Koshy Journal: JAMA Otolaryngol Head Neck Surg Date: 2017-07-01 Impact factor: 6.223
Authors: Ari J Rosenberg; Nishant Agrawal; Alexander T Pearson; Zhen Gooi; Elizabeth Blair; Louis Portugal; John F Cursio; Aditya Juloori; Jeffrey Chin; Kathryn Rouse; Victoria M Villaflor; Tanguy Y Seiwert; Evgeny Izumchenko; Mark W Lingen; Daniel J Haraf; Everett E Vokes Journal: Br J Cancer Date: 2022-08-09 Impact factor: 9.075
Authors: Ari J Rosenberg; Nishant Agrawal; Alexander Pearson; Zhen Gooi; Elizabeth Blair; John Cursio; Aditya Juloori; Daniel Ginat; Adam Howard; Jeffrey Chin; Sara Kochanny; Corey Foster; Nicole Cipriani; Mark Lingen; Evgeny Izumchenko; Tanguy Y Seiwert; Daniel Haraf; Everett E Vokes Journal: Oral Oncol Date: 2021-10-18 Impact factor: 5.972
Authors: Ambika Parmar; Michaelina Macluskey; Niall Mc Goldrick; David I Conway; Anne-Marie Glenny; Janet E Clarkson; Helen V Worthington; Kelvin Kw Chan Journal: Cochrane Database Syst Rev Date: 2021-12-20
Authors: Mai Takahashi; Michael Hwang; Krysztof Misiukiewicz; Vishal Gupta; Brett A Miles; Richard Bakst; Eric Genden; Isaiah Selkridge; John Botzler; Vruti Virani; Erin Moshier; Marcelo R Bonomi; Marshall R Posner Journal: Front Oncol Date: 2022-04-08 Impact factor: 5.738