TY - JOUR
T1 - Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer
T2 - A Literature-Based Systematic Review and Meta-Analysis
AU - Cremolini, Chiara
AU - Antoniotti, Carlotta
AU - Pietrantonio, Filippo
AU - Berenato, Rosa
AU - Tampellini, Marco
AU - Baratelli, Chiara
AU - Salvatore, Lisa
AU - Marmorino, Federica
AU - Borelli, Beatrice
AU - Nichetti, Federico
AU - Bironzo, Paolo
AU - Sonetto, Cristina
AU - Bartolomeo, Maria Di
AU - de Braud, Filippo
AU - Loupakis, Fotios
AU - Falcone, Alfredo
AU - Maio, Massimo Di
PY - 2016/11/15
Y1 - 2016/11/15
N2 - Purpose: To evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).Materials and Methods: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R2).Results: Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were +0.65 months (range, -2.4 to +3.4) for the median PFS and +0.7 months (range, -5.8 to +3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R2=0.5387, p=0.0002) and poor correlation (R=0.1693, R2=0.029, p=0.48) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.Conclusion: Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.
AB - Purpose: To evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).Materials and Methods: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R2).Results: Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were +0.65 months (range, -2.4 to +3.4) for the median PFS and +0.7 months (range, -5.8 to +3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R2=0.5387, p=0.0002) and poor correlation (R=0.1693, R2=0.029, p=0.48) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.Conclusion: Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.
KW - Journal Article
U2 - 10.4143/crt.2016.249
DO - 10.4143/crt.2016.249
M3 - Article
C2 - 27857020
JO - Cancer Research and Treatment
JF - Cancer Research and Treatment
SN - 1598-2998
ER -