Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3

D. P. Modest; T. Denecke; J. Pratschke; I. Ricard; H. Lang; M. Bemelmans; T. Becker; M. Rentsch; D. Seehofer; C. J. Bruns; B. Gebauer; H. I. Modest; S. Held; G. Folprecht; V. Heinemann; U. P. Neumann

doi:10.1016/j.ejca.2017.10.028

Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3

D. P. Modest^*, T. Denecke, J. Pratschke, I. Ricard, H. Lang, M. Bemelmans, T. Becker, M. Rentsch, D. Seehofer, C. J. Bruns, B. Gebauer, H. I. Modest, S. Held, G. Folprecht, V. Heinemann, U. P. Neumann

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. Patients and methods: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Results: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Conclusions: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for preplanned and continuous evaluation for metastatic resection in high-volume centres. (C) 2017 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	77-86
Number of pages	10
Journal	European Journal of Cancer
Volume	88
DOIs	https://doi.org/10.1016/j.ejca.2017.10.028
Publication status	Published - 1 Jan 2018

Keywords

Metastatic colorectal cancer
Resection
Conversion therapy
Cetuximab
Bevacizumab
Surgery
EXPERT CONSENSUS STATEMENT
LIVER METASTASES
PHASE-3 TRIAL
OPEN-LABEL
RESECTION
SURVIVAL
SURGERY
HEPATECTOMY
THERAPIES
DISEASE

Access to Document

10.1016/j.ejca.2017.10.028

Cite this

Modest, D. P., Denecke, T., Pratschke, J., Ricard, I., Lang, H., Bemelmans, M., Becker, T., Rentsch, M., Seehofer, D., Bruns, C. J., Gebauer, B., Modest, H. I., Held, S., Folprecht, G., Heinemann, V., & Neumann, U. P. (2018). Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3. European Journal of Cancer, 88, 77-86. https://doi.org/10.1016/j.ejca.2017.10.028

@article{12a9111a1cac4dabb48c2e22c76f351e,

title = "Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3",

abstract = "Background: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. Patients and methods: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Results: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Conclusions: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for preplanned and continuous evaluation for metastatic resection in high-volume centres. (C) 2017 Elsevier Ltd. All rights reserved.",

keywords = "Metastatic colorectal cancer, Resection, Conversion therapy, Cetuximab, Bevacizumab, Surgery, EXPERT CONSENSUS STATEMENT, LIVER METASTASES, PHASE-3 TRIAL, OPEN-LABEL, RESECTION, SURVIVAL, SURGERY, HEPATECTOMY, THERAPIES, DISEASE",

author = "Modest, {D. P.} and T. Denecke and J. Pratschke and I. Ricard and H. Lang and M. Bemelmans and T. Becker and M. Rentsch and D. Seehofer and Bruns, {C. J.} and B. Gebauer and Modest, {H. I.} and S. Held and G. Folprecht and V. Heinemann and Neumann, {U. P.}",

year = "2018",

month = jan,

day = "1",

doi = "10.1016/j.ejca.2017.10.028",

language = "English",

volume = "88",

pages = "77--86",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "ELSEVIER SCI LTD",

}

Modest, DP, Denecke, T, Pratschke, J, Ricard, I, Lang, H, Bemelmans, M, Becker, T, Rentsch, M, Seehofer, D, Bruns, CJ, Gebauer, B, Modest, HI, Held, S, Folprecht, G, Heinemann, V & Neumann, UP 2018, 'Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3', European Journal of Cancer, vol. 88, pp. 77-86. https://doi.org/10.1016/j.ejca.2017.10.028

TY - JOUR

T1 - Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3

AU - Modest, D. P.

AU - Denecke, T.

AU - Pratschke, J.

AU - Ricard, I.

AU - Lang, H.

AU - Bemelmans, M.

AU - Becker, T.

AU - Rentsch, M.

AU - Seehofer, D.

AU - Bruns, C. J.

AU - Gebauer, B.

AU - Modest, H. I.

AU - Held, S.

AU - Folprecht, G.

AU - Heinemann, V.

AU - Neumann, U. P.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. Patients and methods: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Results: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Conclusions: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for preplanned and continuous evaluation for metastatic resection in high-volume centres. (C) 2017 Elsevier Ltd. All rights reserved.

AB - Background: The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. Patients and methods: This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Results: Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Conclusions: Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for preplanned and continuous evaluation for metastatic resection in high-volume centres. (C) 2017 Elsevier Ltd. All rights reserved.

KW - Metastatic colorectal cancer

KW - Resection

KW - Conversion therapy

KW - Cetuximab

KW - Bevacizumab

KW - Surgery

KW - EXPERT CONSENSUS STATEMENT

KW - LIVER METASTASES

KW - PHASE-3 TRIAL

KW - OPEN-LABEL

KW - RESECTION

KW - SURVIVAL

KW - SURGERY

KW - HEPATECTOMY

KW - THERAPIES

KW - DISEASE

U2 - 10.1016/j.ejca.2017.10.028

DO - 10.1016/j.ejca.2017.10.028

M3 - Article

C2 - 29195117

SN - 0959-8049

VL - 88

SP - 77

EP - 86

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -