Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma

A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205)

Madhur K. Garg, Fengmin Zhao, Joseph A. Sparano, Joel Palefsky, Richard Whittington, Edith P. Mitchell, Mary F. Mulcahy, Karin I. Armstrong, Nassim H. Nabbout, Shalom Kalnicki, Bassel F. El-Rayes, Adedayo A. Onitilo, Daniel J. Moriarty, Thomas J. Fitzgerald, Al B. Benson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight onceweekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided a, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.

Original languageEnglish (US)
Pages (from-to)718-726
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number7
DOIs
StatePublished - Mar 1 2017

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Chemoradiotherapy
Radiology
Anal Canal
Squamous Cell Carcinoma
Papillomaviridae
Carcinoma
Research
Neoplasms
Radiotherapy
Poisons
Kaplan-Meier Estimate
Virus Diseases
Fluorouracil
Cisplatin
Disease-Free Survival
Lymph Nodes
Cetuximab
Survival
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Garg, Madhur K. ; Zhao, Fengmin ; Sparano, Joseph A. ; Palefsky, Joel ; Whittington, Richard ; Mitchell, Edith P. ; Mulcahy, Mary F. ; Armstrong, Karin I. ; Nabbout, Nassim H. ; Kalnicki, Shalom ; El-Rayes, Bassel F. ; Onitilo, Adedayo A. ; Moriarty, Daniel J. ; Fitzgerald, Thomas J. ; Benson, Al B. / Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma : A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205). In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 7. pp. 718-726.
@article{338a90fc261b46d09ea312907553631d,
title = "Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma: A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205)",
abstract = "Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight onceweekly doses of concurrent cetuximab. The study was designed to detect at least a 50{\%} reduction in 3-year LRF rate (one-sided a, 0.10; power 90{\%}), assuming a 35{\%} LRF rate from historical data. Results Poor risk features included stage III disease in 64{\%} and male sex in 20{\%}. The 3-year LRF rate was 23{\%} (95{\%} CI, 13{\%} to 36{\%}; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21{\%} (95{\%} CI, 7{\%} to 26{\%}) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68{\%} (95{\%} CI, 55{\%} to 79{\%}) for progression-free survival and 83{\%} (95{\%} CI, 71{\%} to 91{\%}) for overall survival. Grade 4 toxicity occurred in 32{\%}, and 5{\%} had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20{\%}, indicating the continued need for more effective and less toxic therapies.",
author = "Garg, {Madhur K.} and Fengmin Zhao and Sparano, {Joseph A.} and Joel Palefsky and Richard Whittington and Mitchell, {Edith P.} and Mulcahy, {Mary F.} and Armstrong, {Karin I.} and Nabbout, {Nassim H.} and Shalom Kalnicki and El-Rayes, {Bassel F.} and Onitilo, {Adedayo A.} and Moriarty, {Daniel J.} and Fitzgerald, {Thomas J.} and Benson, {Al B.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1200/JCO.2016.69.1667",
language = "English (US)",
volume = "35",
pages = "718--726",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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}

Garg, MK, Zhao, F, Sparano, JA, Palefsky, J, Whittington, R, Mitchell, EP, Mulcahy, MF, Armstrong, KI, Nabbout, NH, Kalnicki, S, El-Rayes, BF, Onitilo, AA, Moriarty, DJ, Fitzgerald, TJ & Benson, AB 2017, 'Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma: A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205)', Journal of Clinical Oncology, vol. 35, no. 7, pp. 718-726. https://doi.org/10.1200/JCO.2016.69.1667

Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma : A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205). / Garg, Madhur K.; Zhao, Fengmin; Sparano, Joseph A.; Palefsky, Joel; Whittington, Richard; Mitchell, Edith P.; Mulcahy, Mary F.; Armstrong, Karin I.; Nabbout, Nassim H.; Kalnicki, Shalom; El-Rayes, Bassel F.; Onitilo, Adedayo A.; Moriarty, Daniel J.; Fitzgerald, Thomas J.; Benson, Al B.

In: Journal of Clinical Oncology, Vol. 35, No. 7, 01.03.2017, p. 718-726.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cetuximab plus chemoradiotherapy in immunocompetent patients with anal carcinoma

T2 - A phase II Eastern cooperative oncology group-American college of radiology imaging network cancer research group trial (E3205)

AU - Garg, Madhur K.

AU - Zhao, Fengmin

AU - Sparano, Joseph A.

AU - Palefsky, Joel

AU - Whittington, Richard

AU - Mitchell, Edith P.

AU - Mulcahy, Mary F.

AU - Armstrong, Karin I.

AU - Nabbout, Nassim H.

AU - Kalnicki, Shalom

AU - El-Rayes, Bassel F.

AU - Onitilo, Adedayo A.

AU - Moriarty, Daniel J.

AU - Fitzgerald, Thomas J.

AU - Benson, Al B.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight onceweekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided a, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.

AB - Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight onceweekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided a, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.

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U2 - 10.1200/JCO.2016.69.1667

DO - 10.1200/JCO.2016.69.1667

M3 - Article

VL - 35

SP - 718

EP - 726

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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