Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: A meta-analysis

Filippo Pietrantonio, Fausto Petrelli, Andrea Coinu, Maria Di Bartolomeo, Karen Borgonovo, Claudia Maggi, Mary Cabiddu, Roberto Iacovelli, Ilaria Bossi, Veronica Lonati, Mara Ghilardi, Filippo De Braud, Sandro Barni

Research output: Contribution to journalArticle

Abstract

Abstract Background Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p = 0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p = 0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.

Original languageEnglish
Article number9390
Pages (from-to)587-594
Number of pages8
JournalEuropean Journal of Cancer
Volume51
Issue number5
DOIs
Publication statusPublished - 2015

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Meta-Analysis
Colorectal Neoplasms
Mutation
Epidermal Growth Factor Receptor
Confidence Intervals
Therapeutics
Disease-Free Survival
Survival
Monoclonal Antibodies
panitumumab
Cetuximab
Drug Therapy

Keywords

  • BRAF mutation
  • Cetuximab
  • Colorectal cancer
  • Meta-analysis
  • Panitumumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab : A meta-analysis. / Pietrantonio, Filippo; Petrelli, Fausto; Coinu, Andrea; Di Bartolomeo, Maria; Borgonovo, Karen; Maggi, Claudia; Cabiddu, Mary; Iacovelli, Roberto; Bossi, Ilaria; Lonati, Veronica; Ghilardi, Mara; De Braud, Filippo; Barni, Sandro.

In: European Journal of Cancer, Vol. 51, No. 5, 9390, 2015, p. 587-594.

Research output: Contribution to journalArticle

Pietrantonio, F, Petrelli, F, Coinu, A, Di Bartolomeo, M, Borgonovo, K, Maggi, C, Cabiddu, M, Iacovelli, R, Bossi, I, Lonati, V, Ghilardi, M, De Braud, F & Barni, S 2015, 'Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: A meta-analysis', European Journal of Cancer, vol. 51, no. 5, 9390, pp. 587-594. https://doi.org/10.1016/j.ejca.2015.01.054
Pietrantonio, Filippo ; Petrelli, Fausto ; Coinu, Andrea ; Di Bartolomeo, Maria ; Borgonovo, Karen ; Maggi, Claudia ; Cabiddu, Mary ; Iacovelli, Roberto ; Bossi, Ilaria ; Lonati, Veronica ; Ghilardi, Mara ; De Braud, Filippo ; Barni, Sandro. / Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab : A meta-analysis. In: European Journal of Cancer. 2015 ; Vol. 51, No. 5. pp. 587-594.
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abstract = "Abstract Background Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95{\%} confidence interval (CI), 0.67-1.14; p = 0.33), OS (HR, 0.91; 95{\%} CI, 0.62-1.34; p = 0.63) and ORR (relative risk, 1.31; 95{\%} CI 0.83-2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.",
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T1 - Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab

T2 - A meta-analysis

AU - Pietrantonio, Filippo

AU - Petrelli, Fausto

AU - Coinu, Andrea

AU - Di Bartolomeo, Maria

AU - Borgonovo, Karen

AU - Maggi, Claudia

AU - Cabiddu, Mary

AU - Iacovelli, Roberto

AU - Bossi, Ilaria

AU - Lonati, Veronica

AU - Ghilardi, Mara

AU - De Braud, Filippo

AU - Barni, Sandro

PY - 2015

Y1 - 2015

N2 - Abstract Background Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p = 0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p = 0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.

AB - Abstract Background Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p = 0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p = 0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.

KW - BRAF mutation

KW - Cetuximab

KW - Colorectal cancer

KW - Meta-analysis

KW - Panitumumab

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