Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma: Eastern Cooperative Oncology Group Trial E3303

Ann Marie Egloff, Ju Whei Lee, Corey J. Langer, Harry Quon, Alec Vaezi, Jennifer R. Grandis, Raja R. Seethala, Lin Wang, Dong M. Shin, Athanassios Argiris, Donghua Yang, Ranee Mehra, John Andrew Ridge, Urjeet A. Patel, Barbara A. Burtness, Arlene A. Forastiere

Research output: Contribution to journalArticle

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Abstract

Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors.

Original languageEnglish (US)
Pages (from-to)5041-5051
Number of pages11
JournalClinical Cancer Research
Volume20
Issue number19
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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Cisplatin
Radiation
Survival
Disease-Free Survival
Radiotherapy
Neoplasms
Maintenance
Confidence Intervals
Squamous Cell Neoplasms
Mucositis
Cetuximab
Carcinoma, squamous cell of head and neck
Head and Neck Neoplasms
Deglutition Disorders
Clinical Protocols
Neutropenia
Disease Progression
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma : Eastern Cooperative Oncology Group Trial E3303. / Marie Egloff, Ann; Lee, Ju Whei; Langer, Corey J.; Quon, Harry; Vaezi, Alec; Grandis, Jennifer R.; Seethala, Raja R.; Wang, Lin; Shin, Dong M.; Argiris, Athanassios; Yang, Donghua; Mehra, Ranee; Andrew Ridge, John; Patel, Urjeet A.; Burtness, Barbara A.; Forastiere, Arlene A.

In: Clinical Cancer Research, Vol. 20, No. 19, 01.10.2014, p. 5041-5051.

Research output: Contribution to journalArticle

Marie Egloff, A, Lee, JW, Langer, CJ, Quon, H, Vaezi, A, Grandis, JR, Seethala, RR, Wang, L, Shin, DM, Argiris, A, Yang, D, Mehra, R, Andrew Ridge, J, Patel, UA, Burtness, BA & Forastiere, AA 2014, 'Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma: Eastern Cooperative Oncology Group Trial E3303', Clinical Cancer Research, vol. 20, no. 19, pp. 5041-5051. https://doi.org/10.1158/1078-0432.CCR-14-0051
Marie Egloff, Ann ; Lee, Ju Whei ; Langer, Corey J. ; Quon, Harry ; Vaezi, Alec ; Grandis, Jennifer R. ; Seethala, Raja R. ; Wang, Lin ; Shin, Dong M. ; Argiris, Athanassios ; Yang, Donghua ; Mehra, Ranee ; Andrew Ridge, John ; Patel, Urjeet A. ; Burtness, Barbara A. ; Forastiere, Arlene A. / Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma : Eastern Cooperative Oncology Group Trial E3303. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 19. pp. 5041-5051.
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title = "Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma: Eastern Cooperative Oncology Group Trial E3303",
abstract = "Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7{\%}), stage T4 48.3{\%} and N2-3 91.7{\%}. Median radiotherapy dose delivered was 70 Gy, 71.6{\%} received all three cycles of cisplatin, and 74.6{\%} received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47{\%} [95{\%} confidence interval (CI), 33{\%}-61{\%}]. Two-year overall survival (OS) was 66{\%} (95{\%} CI, 53{\%}-77{\%}); median OS was not reached. Response rate was 66.7{\%}. Most common grade ≥3 toxicities included mucositis (55{\%}), dysphagia (46{\%}), and neutropenia (26{\%}); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors.",
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T1 - Phase II study of cetuximab in combination with cisplatin and radiation in Unresectable, locally advanced head and neck squamous cell carcinoma

T2 - Eastern Cooperative Oncology Group Trial E3303

AU - Marie Egloff, Ann

AU - Lee, Ju Whei

AU - Langer, Corey J.

AU - Quon, Harry

AU - Vaezi, Alec

AU - Grandis, Jennifer R.

AU - Seethala, Raja R.

AU - Wang, Lin

AU - Shin, Dong M.

AU - Argiris, Athanassios

AU - Yang, Donghua

AU - Mehra, Ranee

AU - Andrew Ridge, John

AU - Patel, Urjeet A.

AU - Burtness, Barbara A.

AU - Forastiere, Arlene A.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors.

AB - Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks x3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%-61%]. Two-year overall survival (OS) was 66% (95% CI, 53%-77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors.

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