Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713

Cynthia Gail Leichman, Shannon L. McDonough, Stephen R. Smalley, Kevin Billingsley, Heinz Josef Lenz, Matthew A. Beldner, Aram F. Hezel, Mario R. Velasco, Katherine A. Guthrie, Charles Blanke, Howard S. Hochster

Research output: Contribution to journalArticle

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Abstract

Cetuximab enhances response in KRAS (KRAS proto-oncogene) wild type metastatic colorectal cancer. This trial selected patients with KRAS wild type rectal cancer to assess added benefit from cetuximab in the neoadjuvant setting. Pathologic complete response (pCR) was the surrogate for benefit. Eighty patients were enrolled targeting a pCR rate of 35%, an outcome that was not achieved. This regimen cannot be recommended for general use. Background: Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patients and Methods: Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. Treatment: induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Results: Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Conclusion: Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.

Original languageEnglish (US)
Pages (from-to)e121-e125
JournalClinical Colorectal Cancer
Volume17
Issue number1
DOIs
StatePublished - Mar 1 2018

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oxaliplatin
Rectal Neoplasms
Induction Chemotherapy
Proto-Oncogenes
Colorectal Neoplasms
Confidence Intervals
Capecitabine
Cetuximab

Keywords

  • Chemotherapy
  • Cooperative group trial
  • KRAS
  • pCR
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer : SWOG 0713. / Leichman, Cynthia Gail; McDonough, Shannon L.; Smalley, Stephen R.; Billingsley, Kevin; Lenz, Heinz Josef; Beldner, Matthew A.; Hezel, Aram F.; Velasco, Mario R.; Guthrie, Katherine A.; Blanke, Charles; Hochster, Howard S.

In: Clinical Colorectal Cancer, Vol. 17, No. 1, 01.03.2018, p. e121-e125.

Research output: Contribution to journalArticle

Leichman, Cynthia Gail ; McDonough, Shannon L. ; Smalley, Stephen R. ; Billingsley, Kevin ; Lenz, Heinz Josef ; Beldner, Matthew A. ; Hezel, Aram F. ; Velasco, Mario R. ; Guthrie, Katherine A. ; Blanke, Charles ; Hochster, Howard S. / Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer : SWOG 0713. In: Clinical Colorectal Cancer. 2018 ; Vol. 17, No. 1. pp. e121-e125.
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title = "Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713",
abstract = "Cetuximab enhances response in KRAS (KRAS proto-oncogene) wild type metastatic colorectal cancer. This trial selected patients with KRAS wild type rectal cancer to assess added benefit from cetuximab in the neoadjuvant setting. Pathologic complete response (pCR) was the surrogate for benefit. Eighty patients were enrolled targeting a pCR rate of 35{\%}, an outcome that was not achieved. This regimen cannot be recommended for general use. Background: Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10{\%} to 20{\%}. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patients and Methods: Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. Treatment: induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90{\%} power given a true pCR rate > 35{\%} at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20{\%}. Results: Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27{\%}; 95{\%} confidence interval [CI], 17{\%}-38{\%}); 19 (25{\%}) had microscopic cancer; 36 (48{\%}) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73{\%} (95{\%} CI, 63{\%}-83{\%}). Conclusion: Our trial did not meet the pCR target of 35{\%}. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.",
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author = "Leichman, {Cynthia Gail} and McDonough, {Shannon L.} and Smalley, {Stephen R.} and Kevin Billingsley and Lenz, {Heinz Josef} and Beldner, {Matthew A.} and Hezel, {Aram F.} and Velasco, {Mario R.} and Guthrie, {Katherine A.} and Charles Blanke and Hochster, {Howard S.}",
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T1 - Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

T2 - SWOG 0713

AU - Leichman, Cynthia Gail

AU - McDonough, Shannon L.

AU - Smalley, Stephen R.

AU - Billingsley, Kevin

AU - Lenz, Heinz Josef

AU - Beldner, Matthew A.

AU - Hezel, Aram F.

AU - Velasco, Mario R.

AU - Guthrie, Katherine A.

AU - Blanke, Charles

AU - Hochster, Howard S.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Cetuximab enhances response in KRAS (KRAS proto-oncogene) wild type metastatic colorectal cancer. This trial selected patients with KRAS wild type rectal cancer to assess added benefit from cetuximab in the neoadjuvant setting. Pathologic complete response (pCR) was the surrogate for benefit. Eighty patients were enrolled targeting a pCR rate of 35%, an outcome that was not achieved. This regimen cannot be recommended for general use. Background: Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patients and Methods: Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. Treatment: induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Results: Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Conclusion: Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.

AB - Cetuximab enhances response in KRAS (KRAS proto-oncogene) wild type metastatic colorectal cancer. This trial selected patients with KRAS wild type rectal cancer to assess added benefit from cetuximab in the neoadjuvant setting. Pathologic complete response (pCR) was the surrogate for benefit. Eighty patients were enrolled targeting a pCR rate of 35%, an outcome that was not achieved. This regimen cannot be recommended for general use. Background: Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patients and Methods: Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. Treatment: induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Results: Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Conclusion: Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.

KW - Chemotherapy

KW - Cooperative group trial

KW - KRAS

KW - pCR

KW - Phase II

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