Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients.

Stefano Cascinu, Gerardo Rosati, Guglielmo Nasti, Sara Lonardi, Alberto Zaniboni, Paolo Marchetti, Francesco Leone, Domenico Bilancia, Rosario Vincenzo Iaffaioli, Vittorina Zagonel, Monica Giordano, Domenico C. Corsi, Francesco Ferrau, Roberto Labianca, Monica Ronzoni, Mario Scartozzi, Francesca Galli

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Abstract

INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). RESULTS: About 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.69-1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95% CI: 0.55-1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. CONCLUSIONS: This trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.
Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalEuropean Journal of Cancer
Volume83
Publication statusPublished - Sep 1 2017

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irinotecan
Gastrointestinal Neoplasms
Disease-Free Survival
Colorectal Neoplasms
Confidence Intervals
Therapeutics
Survival
Bevacizumab
Cetuximab

Keywords

  • Aged, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Bevacizumab/administration & dosage, Camptothecin/administration & dosage/analogs & derivatives, Carcinoma/drug therapy, Cetuximab/administration & dosage, Colorectal Neoplasms/*drug therapy, Disease-Free Survival, Female, Fluorouracil/administration & dosage, Humans, Kaplan-Meier Estimate, Leucovorin/administration & dosage, Male, Middle Aged, Organoplatinum Compounds/administration & dosage, *Cetuximab, *K-RAS wild type, *Metastatic colorectal cancer, *Treatment sequence, *Treatment strategy

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Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. / Cascinu, Stefano; Rosati, Gerardo; Nasti, Guglielmo; Lonardi, Sara; Zaniboni, Alberto; Marchetti, Paolo; Leone, Francesco; Bilancia, Domenico; Iaffaioli, Rosario Vincenzo; Zagonel, Vittorina; Giordano, Monica; Corsi, Domenico C.; Ferrau, Francesco; Labianca, Roberto; Ronzoni, Monica; Scartozzi, Mario; Galli, Francesca.

In: European Journal of Cancer, Vol. 83, 01.09.2017, p. 106-115.

Research output: Contribution to journalArticle

Cascinu, Stefano ; Rosati, Gerardo ; Nasti, Guglielmo ; Lonardi, Sara ; Zaniboni, Alberto ; Marchetti, Paolo ; Leone, Francesco ; Bilancia, Domenico ; Iaffaioli, Rosario Vincenzo ; Zagonel, Vittorina ; Giordano, Monica ; Corsi, Domenico C. ; Ferrau, Francesco ; Labianca, Roberto ; Ronzoni, Monica ; Scartozzi, Mario ; Galli, Francesca. / Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients. In: European Journal of Cancer. 2017 ; Vol. 83. pp. 106-115.
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abstract = "INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). RESULTS: About 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95{\%} confidence interval [CI]: 0.69-1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95{\%} CI: 0.55-1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. CONCLUSIONS: This trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.",
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T1 - Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients.

AU - Cascinu, Stefano

AU - Rosati, Gerardo

AU - Nasti, Guglielmo

AU - Lonardi, Sara

AU - Zaniboni, Alberto

AU - Marchetti, Paolo

AU - Leone, Francesco

AU - Bilancia, Domenico

AU - Iaffaioli, Rosario Vincenzo

AU - Zagonel, Vittorina

AU - Giordano, Monica

AU - Corsi, Domenico C.

AU - Ferrau, Francesco

AU - Labianca, Roberto

AU - Ronzoni, Monica

AU - Scartozzi, Mario

AU - Galli, Francesca

PY - 2017/9/1

Y1 - 2017/9/1

N2 - INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). RESULTS: About 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.69-1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95% CI: 0.55-1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. CONCLUSIONS: This trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.

AB - INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). RESULTS: About 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.69-1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95% CI: 0.55-1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. CONCLUSIONS: This trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.

KW - Aged, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Bevacizumab/administration & dosage, Camptothecin/administration & dosage/analogs & derivatives, Carcinoma/drug therapy, Cetux

M3 - Article

VL - 83

SP - 106

EP - 115

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -