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 language | English |
|---|---|
| Article number | 9390 |
| Pages (from-to) | 587-594 |
| Number of pages | 8 |
| Journal | European Journal of Cancer |
| Volume | 51 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2015 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84925105975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925105975&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2015.01.054
DO - 10.1016/j.ejca.2015.01.054
M3 - Article
C2 - 25673558
AN - SCOPUS:84925105975
VL - 51
SP - 587
EP - 594
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 5
M1 - 9390
ER -