Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis
Cancer Research and Treatment 2017³â 49±Ç 3È£ p.834 ~ p.845
(Cremolini Chiara) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Antoniotti Carlotta) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Pietrantonio Filippo) - Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department
(Berenato Rosa) - Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department
(Tampellini Marco) - University of Turin A.O.U. San Luigi Gonzaga Department of Oncology
(Baratelli Chiara) - University of Turin A.O.U. San Luigi Gonzaga Department of Oncology
(Salvatore Lisa) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Marmorino Federica) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Borelli Beatrice) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Nichetti Federico) - Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department
(Bironzo Paolo) - University of Turin A.O.U. San Luigi Gonzaga Department of Oncology
(Sonetto Cristina) - University of Turin A.O.U. San Luigi Gonzaga Department of Oncology
(Di Bartolomeo Maria) - Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department
(De Braud Filippo) - Fondazione IRCCS Istituto Nazionale dei Tumori Medical Oncology Department
(Loupakis Fotios) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Falcone Alfredo) - University of Pisa Department of Translational Research and New Technologies in Medicine
(Di Maio Massimo) - University of Turin A.O. Ordine Mauriziano Department of Oncology
Abstract
Purpose: The purpose of this study was 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=0.539, p < 0.001) and poor correlation (R=0.169, R2=0.029, p=0.476) 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.
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Colorectal neoplasms, Biomarkers, Molecular targeted therapy
KMID :
0939920170490030834
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Overall, there was a moderate correlation between PFS and OS (R=0.632, R2=0.399, p < 0.001). ; PFS and ORR showed moderate (R=0.734, R2=0.539, p < 0.001) and poor correlation (R=0.169, R2=0.029, p=0.476) with OS;