Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Eduardo Díaz-Rubio; Auxiliadora Gómez-España; Bartomeu Massutí; Javier Sastre; Margarita Reboredo; José Luis Manzano; Fernando Rivera; M. José Safont; Clara Montagut; Encarnación González; Manuel Benavides; Eugenio Marcuello; Andrés Cervantes; Purificación Martínez de Prado; Carlos Fernández-Martos; Antonio Arrivi; Inmaculada Bando; Enrique Aranda; A. Gómez; B. Massutí; A. Yuste; E. Díaz Rubio; J. Sastre; M. Valladares; A. Abad; F. Rivera; M. J. Safont; M. Gallén; E. González; M. Benavides; E. Marcuello; M. Tobeña; A. Cervantes; P. Martínez de Prado; C. Fernández-Martos; A. Arrivi; A. López-Ladrón; A. Lacasta; M. Llanos; J. Remón; A. Anton; J. M. Vicent; A. Galán; R. Dueñas; J. M. Tabernero; H. Manzano; M. J. Gómez; J. Alfaro; F. Losa; P. Escudero; T. García; J. L. García López; M. L. García de Paredes; A. Velasco; D. Almenar; R. Vera; J. L. García Puche; A. Carrato; A. Rodriguez Lescure; E. Jiménez; V. Alberola; J. García-Foncillas; M. Constenla; A. Ruiz; P. Bueso; E. Cabrera; L. del Río; J. Ponce; A. Oltra; T. Checa; A. Etxeberría; C. Alonso

doi:10.1371/journal.pone.0047345

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Eduardo Díaz-Rubio, Auxiliadora Gómez-España, Bartomeu Massutí, Javier Sastre, Margarita Reboredo, José Luis Manzano, Fernando Rivera, M. José Safont, Clara Montagut, Encarnación González, Manuel Benavides, Eugenio Marcuello, Andrés Cervantes, Purificación Martínez de Prado, Carlos Fernández-Martos, Antonio Arrivi, Inmaculada Bando, Enrique Aranda, A. Gómez, B. MassutíA. Yuste, E. Díaz Rubio, J. Sastre, M. Valladares, A. Abad, F. Rivera, M. J. Safont, M. Gallén, E. González, M. Benavides, E. Marcuello, M. Tobeña, A. Cervantes, P. Martínez de Prado, C. Fernández-Martos, A. Arrivi, A. López-Ladrón, A. Lacasta, M. Llanos, J. Remón, A. Anton, J. M. Vicent, A. Galán, R. Dueñas, J. M. Tabernero, H. Manzano, M. J. Gómez, J. Alfaro, F. Losa, P. Escudero, T. García, J. L. García López, M. L. García de Paredes, A. Velasco, D. Almenar, R. Vera, J. L. García Puche, A. Carrato, A. Rodriguez Lescure, E. Jiménez, V. Alberola, J. García-Foncillas, M. Constenla, A. Ruiz, P. Bueso, E. Cabrera, L. del Río, J. Ponce, A. Oltra, T. Checa, A. Etxeberría, C. Alonso

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Résumé

Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

langue originale	Anglais
Numéro d'article	e47345
journal	PLoS ONE
Volume	7
Numéro de publication	10
Les DOIs	https://doi.org/10.1371/journal.pone.0047345
état	Publié - 12 oct. 2012
Modification externe	Oui

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10.1371/journal.pone.0047345

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Díaz-Rubio, E., Gómez-España, A., Massutí, B., Sastre, J., Reboredo, M., Manzano, J. L., Rivera, F., Safont, M. J., Montagut, C., González, E., Benavides, M., Marcuello, E., Cervantes, A., Martínez de Prado, P., Fernández-Martos, C., Arrivi, A., Bando, I., Aranda, E., Gómez, A., ... Alonso, C. (2012). Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study. PLoS ONE, 7(10), Article e47345. https://doi.org/10.1371/journal.pone.0047345

@article{2d568ee5b87947d9b569f151292ba172,

title = "Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study",

abstract = "Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.",

author = "Eduardo D{\'i}az-Rubio and Auxiliadora G{\'o}mez-Espa{\~n}a and Bartomeu Massut{\'i} and Javier Sastre and Margarita Reboredo and Manzano, {Jos{\'e} Luis} and Fernando Rivera and Safont, {M. Jos{\'e}} and Clara Montagut and Encarnaci{\'o}n Gonz{\'a}lez and Manuel Benavides and Eugenio Marcuello and Andr{\'e}s Cervantes and {Mart{\'i}nez de Prado}, Purificaci{\'o}n and Carlos Fern{\'a}ndez-Martos and Antonio Arrivi and Inmaculada Bando and Enrique Aranda and A. G{\'o}mez and B. Massut{\'i} and A. Yuste and Rubio, {E. D{\'i}az} and J. Sastre and M. Valladares and A. Abad and F. Rivera and Safont, {M. J.} and M. Gall{\'e}n and E. Gonz{\'a}lez and M. Benavides and E. Marcuello and M. Tobe{\~n}a and A. Cervantes and {Mart{\'i}nez de Prado}, P. and C. Fern{\'a}ndez-Martos and A. Arrivi and A. L{\'o}pez-Ladr{\'o}n and A. Lacasta and M. Llanos and J. Rem{\'o}n and A. Anton and Vicent, {J. M.} and A. Gal{\'a}n and R. Due{\~n}as and Tabernero, {J. M.} and H. Manzano and G{\'o}mez, {M. J.} and J. Alfaro and F. Losa and P. Escudero and T. Garc{\'i}a and {Garc{\'i}a L{\'o}pez}, {J. L.} and {Garc{\'i}a de Paredes}, {M. L.} and A. Velasco and D. Almenar and R. Vera and {Garc{\'i}a Puche}, {J. L.} and A. Carrato and Lescure, {A. Rodriguez} and E. Jim{\'e}nez and V. Alberola and J. Garc{\'i}a-Foncillas and M. Constenla and A. Ruiz and P. Bueso and E. Cabrera and {del R{\'i}o}, L. and J. Ponce and A. Oltra and T. Checa and A. Etxeberr{\'i}a and C. Alonso",

year = "2012",

month = oct,

day = "12",

doi = "10.1371/journal.pone.0047345",

language = "English",

volume = "7",

journal = "PLoS ONE",

issn = "1932-6203",

number = "10",

}

Díaz-Rubio, E, Gómez-España, A, Massutí, B, Sastre, J, Reboredo, M, Manzano, JL, Rivera, F, Safont, MJ, Montagut, C, González, E, Benavides, M, Marcuello, E, Cervantes, A, Martínez de Prado, P, Fernández-Martos, C, Arrivi, A, Bando, I, Aranda, E, Gómez, A, Massutí, B, Yuste, A, Rubio, ED, Sastre, J, Valladares, M, Abad, A, Rivera, F, Safont, MJ, Gallén, M, González, E, Benavides, M, Marcuello, E, Tobeña, M, Cervantes, A, Martínez de Prado, P, Fernández-Martos, C, Arrivi, A, López-Ladrón, A, Lacasta, A, Llanos, M, Remón, J, Anton, A, Vicent, JM, Galán, A, Dueñas, R, Tabernero, JM, Manzano, H, Gómez, MJ, Alfaro, J, Losa, F, Escudero, P, García, T, García López, JL, García de Paredes, ML, Velasco, A, Almenar, D, Vera, R, García Puche, JL, Carrato, A, Lescure, AR, Jiménez, E, Alberola, V, García-Foncillas, J, Constenla, M, Ruiz, A, Bueso, P, Cabrera, E, del Río, L, Ponce, J, Oltra, A, Checa, T, Etxeberría, A & Alonso, C 2012, 'Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study', PLoS ONE, VOL. 7, Numéro 10, e47345. https://doi.org/10.1371/journal.pone.0047345

TY - JOUR

T1 - Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab

T2 - A TTD Group Cooperative Study

AU - Díaz-Rubio, Eduardo

AU - Gómez-España, Auxiliadora

AU - Massutí, Bartomeu

AU - Sastre, Javier

AU - Reboredo, Margarita

AU - Manzano, José Luis

AU - Rivera, Fernando

AU - Safont, M. José

AU - Montagut, Clara

AU - González, Encarnación

AU - Benavides, Manuel

AU - Marcuello, Eugenio

AU - Cervantes, Andrés

AU - Martínez de Prado, Purificación

AU - Fernández-Martos, Carlos

AU - Arrivi, Antonio

AU - Bando, Inmaculada

AU - Aranda, Enrique

AU - Gómez, A.

AU - Massutí, B.

AU - Yuste, A.

AU - Rubio, E. Díaz

AU - Sastre, J.

AU - Valladares, M.

AU - Abad, A.

AU - Rivera, F.

AU - Safont, M. J.

AU - Gallén, M.

AU - González, E.

AU - Benavides, M.

AU - Marcuello, E.

AU - Tobeña, M.

AU - Cervantes, A.

AU - Martínez de Prado, P.

AU - Fernández-Martos, C.

AU - Arrivi, A.

AU - López-Ladrón, A.

AU - Lacasta, A.

AU - Llanos, M.

AU - Remón, J.

AU - Anton, A.

AU - Vicent, J. M.

AU - Galán, A.

AU - Dueñas, R.

AU - Tabernero, J. M.

AU - Manzano, H.

AU - Gómez, M. J.

AU - Alfaro, J.

AU - Losa, F.

AU - Escudero, P.

AU - García, T.

AU - García López, J. L.

AU - García de Paredes, M. L.

AU - Velasco, A.

AU - Almenar, D.

AU - Vera, R.

AU - García Puche, J. L.

AU - Carrato, A.

AU - Lescure, A. Rodriguez

AU - Jiménez, E.

AU - Alberola, V.

AU - García-Foncillas, J.

AU - Constenla, M.

AU - Ruiz, A.

AU - Bueso, P.

AU - Cabrera, E.

AU - del Río, L.

AU - Ponce, J.

AU - Oltra, A.

AU - Checa, T.

AU - Etxeberría, A.

AU - Alonso, C.

PY - 2012/10/12

Y1 - 2012/10/12

N2 - Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

AB - Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

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U2 - 10.1371/journal.pone.0047345

DO - 10.1371/journal.pone.0047345

M3 - Article

C2 - 23174912

AN - SCOPUS:84867411491

SN - 1932-6203

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 10

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