Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer. Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab
BACKGROUND Polychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer ( CRC ) . We examined the relation between progression-free survival ( PFS ) , post-progression survival ( PPS ) and overall survival ( OS ) in trials of  modern ( oxaliplatin- and irinotecan-based ) chemotherapy alone or with targeted therapies for advanced CRC . We also evaluated surrogacy of PFS and OS . PATIENTS AND METHODS A PubMed search identified 34 r and omized trials . We split the OS , PFS and PPS and evaluated the correlation between OS and either PFS or PPS . RESULTS The median PPS and PFS were 10.75 and 8.4 months , respectively . For all trials , PPS was strongly associated with OS [ regression coefficient (R2)=0.8 ; Spearman 's rank correlation coefficient (r)=0.88 ] , whereas PFS was moderately associated with OS (R2)=0.43 ; r=0.64 ) . In trials with targeted therapies , the correlation of PPS with OS was 0.88 . However , across all trials , correlation between differences in median PFS ( ΔPFS ) and median OS ( ΔOS ) is 0.59 ( P=0.0007 ) , confirming PFS/OS surrogacy . CONCLUSION Our findings indicate that in recent first-line , phase III , trials , OS becomes more associated with PPS than PFS . However , improvements in PFS are strongly associated with improvements in OS . In this setting so , PFS may be an appropriate surrogate for OS The aim of the study was to evaluate the association of vascular endothelial growth factor ( VEGF ) genotypes with treatment efficacy in a r and omized trial . This study compared two chemotherapy regimens ( FOLFIRI versus XELIRI ) combined with bevacizumab , as first-line treatment for metastatic colorectal cancer . DNA was extracted from blood sample s of 173 patients participating in the trial . Genotyping was performed for selected SNPs ( VEGF−1154 , + 936 , −634 , −2578 and −1498 ) . All c and i date genotypes were evaluated for associations with overall survival ( OS ) , progression-free survival ( PFS ) and response rate ( RR ) . There were no significant differences with respect to the distribution of genotypes in the treatment groups . The VEGF−1154 GG genotype was more frequent in patients not responding to treatment compared with responders ( 65.5 versus 39.8 % , P=0.032 ) . Furthermore , the VEGF−1154 GG genotype was associated with inferior median OS compared with GA ( hazards ratio=1.68 ; 95 % confidence interval : 1.10–2.57 ; P=0.016 ) or with the alternative genotypes ( GA and AA ) combined ( hazards ratio=1.62 ; 95 % confidence interval : 1.09–2.40 ; P=0.017 ) . In multivariate analysis , the VEGF−1154 GG genotype remained a significant adverse factor for OS . Our results support the potential predictive ability of VEGF genotypes in patients with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus bevacizumab  , in terms of RR and OS . However , current results should be vali date d prospect ively , in larger cohorts
First-line chemotherapy + bevacizumab ( BEV ) is one of the st and ards of care in advanced colorectal cancer ( CRC ) .
Contrary to anti-EGFR agents , it is currently not possible to identify the ideal c and i date for BEV-based chemotherapy due to the lack of predictors of outcomes .
The aim of this study was to perform a systematic review of risk factors for survival after B-based chemotherapy for CRC .