Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): A randomized, multicenter, phase II trial SAKK 41/07

D. Helbling, G. Bodoky, O. Gautschi, H. Sun, F. Bosman, B. Gloor, R. Burkhard, R. Winterhalder, A. Madlung, D. Rauch, P. Saletti, L. Widmer, M. Borner, D. Baertschi, P. Yan, J. Benhattar, E. O. Leibundgut, S. Bougel, D. Koeberle

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Abstract

Background: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). Patients and methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Results: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). Conclusions: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Original languageEnglish
Article numbermds519
Pages (from-to)718-725
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Chemoradiotherapy
Rectal Neoplasms
Confidence Intervals
panitumumab
Neoplasms
Anastomotic Leak
Neoadjuvant Therapy
Poisons
Epidermal Growth Factor Receptor
Multicenter Studies
Diarrhea

Keywords

  • Capecitabine
  • Chemoradiotherapy
  • Panitumumab
  • Radiotherapy
  • Rectal cancer
  • Wild-type KRAS

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC) : A randomized, multicenter, phase II trial SAKK 41/07. / Helbling, D.; Bodoky, G.; Gautschi, O.; Sun, H.; Bosman, F.; Gloor, B.; Burkhard, R.; Winterhalder, R.; Madlung, A.; Rauch, D.; Saletti, P.; Widmer, L.; Borner, M.; Baertschi, D.; Yan, P.; Benhattar, J.; Leibundgut, E. O.; Bougel, S.; Koeberle, D.

In: Annals of Oncology, Vol. 24, No. 3, mds519, 03.2013, p. 718-725.

Research output: Contribution to journalArticle

Helbling, D, Bodoky, G, Gautschi, O, Sun, H, Bosman, F, Gloor, B, Burkhard, R, Winterhalder, R, Madlung, A, Rauch, D, Saletti, P, Widmer, L, Borner, M, Baertschi, D, Yan, P, Benhattar, J, Leibundgut, EO, Bougel, S & Koeberle, D 2013, 'Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): A randomized, multicenter, phase II trial SAKK 41/07', Annals of Oncology, vol. 24, no. 3, mds519, pp. 718-725. https://doi.org/10.1093/annonc/mds519
Helbling, D. ; Bodoky, G. ; Gautschi, O. ; Sun, H. ; Bosman, F. ; Gloor, B. ; Burkhard, R. ; Winterhalder, R. ; Madlung, A. ; Rauch, D. ; Saletti, P. ; Widmer, L. ; Borner, M. ; Baertschi, D. ; Yan, P. ; Benhattar, J. ; Leibundgut, E. O. ; Bougel, S. ; Koeberle, D. / Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC) : A randomized, multicenter, phase II trial SAKK 41/07. In: Annals of Oncology. 2013 ; Vol. 24, No. 3. pp. 718-725.
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abstract = "Background: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). Patients and methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Results: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53{\%}) treated with P + CRT [95{\%} confidence interval (CI) 36{\%}-69{\%}] versus 9 patients (32{\%}) treated with CRT alone (95{\%} CI: 16{\%}-52{\%}). pCR was achieved in 4 (10{\%}) and 5 (18{\%}) patients, and pNCR in 17 (43{\%}) and 4 (14{\%}) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10{\%}/6{\%}) and anastomotic leakage (15{\%}/4{\%}). Conclusions: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.",
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T1 - Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC)

T2 - A randomized, multicenter, phase II trial SAKK 41/07

AU - Helbling, D.

AU - Bodoky, G.

AU - Gautschi, O.

AU - Sun, H.

AU - Bosman, F.

AU - Gloor, B.

AU - Burkhard, R.

AU - Winterhalder, R.

AU - Madlung, A.

AU - Rauch, D.

AU - Saletti, P.

AU - Widmer, L.

AU - Borner, M.

AU - Baertschi, D.

AU - Yan, P.

AU - Benhattar, J.

AU - Leibundgut, E. O.

AU - Bougel, S.

AU - Koeberle, D.

PY - 2013/3

Y1 - 2013/3

N2 - Background: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). Patients and methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Results: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). Conclusions: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

AB - Background: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). Patients and methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). Results: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). Conclusions: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

KW - Capecitabine

KW - Chemoradiotherapy

KW - Panitumumab

KW - Radiotherapy

KW - Rectal cancer

KW - Wild-type KRAS

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DO - 10.1093/annonc/mds519

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C2 - 23139259

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JO - Annals of Oncology

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