Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: A multicenter study in Japan

Hiroshi Saeki, Yasunori Emi, Ryuichi Kumashiro, Hajime Otsu, Hiroyuki Kawano, Koji Ando, Satoshi Ida, Yasue Kimura, Eriko Tokunaga, Eiji Oki, Masaru Morita, Mototsugu Shimokawa, Yoshihiko Maehara

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Abstract

Purposes: This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy. Methods: The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing. Results: A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018). Conclusions: The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.

Original languageEnglish
Pages (from-to)1457-1464
Number of pages8
JournalSurgery today
Volume44
Issue number8
DOIs
Publication statusPublished - Aug 2014

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Multicenter Studies
Colorectal Neoplasms
Japan
Genotype
Mutation
Therapeutics
Exanthema
Cetuximab
Acne Vulgaris
Neutropenia
Anemia
Neoplasms
Retrospective Studies
Survival
Population

All Science Journal Classification (ASJC) codes

  • Surgery

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Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer : A multicenter study in Japan. / Saeki, Hiroshi; Emi, Yasunori; Kumashiro, Ryuichi; Otsu, Hajime; Kawano, Hiroyuki; Ando, Koji; Ida, Satoshi; Kimura, Yasue; Tokunaga, Eriko; Oki, Eiji; Morita, Masaru; Shimokawa, Mototsugu; Maehara, Yoshihiko.

In: Surgery today, Vol. 44, No. 8, 08.2014, p. 1457-1464.

Research output: Contribution to journalArticle

Saeki, Hiroshi ; Emi, Yasunori ; Kumashiro, Ryuichi ; Otsu, Hajime ; Kawano, Hiroyuki ; Ando, Koji ; Ida, Satoshi ; Kimura, Yasue ; Tokunaga, Eriko ; Oki, Eiji ; Morita, Masaru ; Shimokawa, Mototsugu ; Maehara, Yoshihiko. / Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer : A multicenter study in Japan. In: Surgery today. 2014 ; Vol. 44, No. 8. pp. 1457-1464.
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abstract = "Purposes: This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy. Methods: The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing. Results: A detailed analysis revealed the presence of 24 wild-type (57.1 {\%}) and 18 mutant tumors (42.9 {\%}). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 {\%}) and nine (13.8 {\%}) patients, respectively. An acne-like rash was observed in 50 patients (76.9 {\%}), and among them three patients (4.6 {\%}) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 {\%} responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018). Conclusions: The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.",
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T1 - Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer

T2 - A multicenter study in Japan

AU - Saeki, Hiroshi

AU - Emi, Yasunori

AU - Kumashiro, Ryuichi

AU - Otsu, Hajime

AU - Kawano, Hiroyuki

AU - Ando, Koji

AU - Ida, Satoshi

AU - Kimura, Yasue

AU - Tokunaga, Eriko

AU - Oki, Eiji

AU - Morita, Masaru

AU - Shimokawa, Mototsugu

AU - Maehara, Yoshihiko

PY - 2014/8

Y1 - 2014/8

N2 - Purposes: This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy. Methods: The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing. Results: A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018). Conclusions: The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.

AB - Purposes: This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy. Methods: The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing. Results: A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018). Conclusions: The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.

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