Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G

Kohei Shitara, Kimio Yonesaka, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Masahiro Tsuda, Toshimi Takano, Hiroyuki Okuda, Tomohiro Nishina, Kazuko Sakai, Kazuto Nishio, Shoji Tokunaga, Takeharu Yamanaka, Narikazu Boku, Ichinosuke Hyodo, Kei Muro

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Abstract

This randomized phase II trial compared panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second-line chemotherapy for wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory to first-line chemotherapy containing oxaliplatin and bevacizumab were randomly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI. Of 121 randomly assigned patients, 117 were eligible. Median overall survival (OS) for panitumumab plus FOLFIRI and bevacizumab plus FOLFIRI were 16.2 and 13.4 months [hazard ratio (HR), 1.16; 95% CI, 0.76–1.77], respectively. Progression-free survival (PFS) was also similar (HR, 1.14; 95% CI, 0.78–1.66). KRAS, NRAS, and BRAF status using ctDNA was successfully examined in 109 patients, and mutations were identified in 19 patients (17.4%). Panitumumab plus FOLFIRI showed favorable survival compared with bevacizumab plus FOLFIRI in WT patients and unfavorable survival in those with mutations (P for interaction = 0.026 in OS and 0.054 in PFS). OS with bevacizumab plus FOLFIRI was better than panitumumab plus FOLFIRI in patients with high serum vascular endothelial growth factor-A (VEGF-A) levels and worse in those with low levels (P for interaction = 0.016). Second-line FOLFIRI plus panitumumab and FOLFIRI plus bevacizumab showed a similar efficacy in patients with WT KRAS exon 2 mCRC. RAS and BRAF mutation in ctDNA could be a negative predictive marker for panitumumab.

Original languageEnglish
Pages (from-to)1843-1850
Number of pages8
JournalCancer Science
Volume107
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

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Colorectal Neoplasms
Survival
Exons
irinotecan
oxaliplatin
Mutation
Disease-Free Survival
DNA
Drug Therapy
Neoplasms
Leucovorin
Bevacizumab
panitumumab
Oncogenes
Fluorouracil
Vascular Endothelial Growth Factor A
Blood Proteins
Biomarkers
Serum

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shitara, K., Yonesaka, K., Denda, T., Yamazaki, K., Moriwaki, T., Tsuda, M., ... Muro, K. (2016). Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. Cancer Science, 107(12), 1843-1850. https://doi.org/10.1111/cas.13098

Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. / Shitara, Kohei; Yonesaka, Kimio; Denda, Tadamichi; Yamazaki, Kentaro; Moriwaki, Toshikazu; Tsuda, Masahiro; Takano, Toshimi; Okuda, Hiroyuki; Nishina, Tomohiro; Sakai, Kazuko; Nishio, Kazuto; Tokunaga, Shoji; Yamanaka, Takeharu; Boku, Narikazu; Hyodo, Ichinosuke; Muro, Kei.

In: Cancer Science, Vol. 107, No. 12, 01.12.2016, p. 1843-1850.

Research output: Contribution to journalArticle

Shitara, K, Yonesaka, K, Denda, T, Yamazaki, K, Moriwaki, T, Tsuda, M, Takano, T, Okuda, H, Nishina, T, Sakai, K, Nishio, K, Tokunaga, S, Yamanaka, T, Boku, N, Hyodo, I & Muro, K 2016, 'Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G', Cancer Science, vol. 107, no. 12, pp. 1843-1850. https://doi.org/10.1111/cas.13098
Shitara, Kohei ; Yonesaka, Kimio ; Denda, Tadamichi ; Yamazaki, Kentaro ; Moriwaki, Toshikazu ; Tsuda, Masahiro ; Takano, Toshimi ; Okuda, Hiroyuki ; Nishina, Tomohiro ; Sakai, Kazuko ; Nishio, Kazuto ; Tokunaga, Shoji ; Yamanaka, Takeharu ; Boku, Narikazu ; Hyodo, Ichinosuke ; Muro, Kei. / Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. In: Cancer Science. 2016 ; Vol. 107, No. 12. pp. 1843-1850.
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