Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer Journal Article


Authors: Sargent, D. J.; Köhne, C. H.; Sanoff, H. K.; Bot, B. M.; Seymour, M. T.; De Gramont, A.; Porschen, R.; Saltz, L. B.; Rougier, P.; Tournigand, C.; Douillard, J. Y.; Stephens, R. J.; Grothey, A.; Goldberg, R. M.
Article Title: Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer
Abstract: Purpose Performance status (PS) is a prognostic factor in patients with metastatic colorectal cancer. Clinical trials typically enroll less than 10% of patients with a PS of 2 (PS2); thus, the benefit of systemic chemotherapy in PS2 patients is uncertain. Patients and Methods Individual data from 6,286 patients (509 PS2 patients) from nine clinical trials were used to compare treatment efficacy by PS. Progression-free survival (PFS), grade ≥ 3 adverse events, 60-day all-cause mortality, overall survival (OS), and response rate (RR) were explored in the full set of nine trials and in the five trials comparing first-line monotherapy with combination therapy. Results Compared with patients with PS of 0 or 1, PS2 patients had significantly higher rates of grade ≥ 3 nausea (8.5% v 16.4%, respectively; P < .0001) and vomiting (7.6% v 11.9%, respectively; P = .006) and 60-day all-cause mortality (2.8% v 12.0%, respectively; P < .0001). PS2 was prognostic for PFS (hazard ratio [HR] = 1.52; P < .0001; median PFS, 7.6 months for PS 0 or 1 v 4.9 months for PS2), OS (HR = 2.18; P < .0001; median OS, 17.3 months for PS 0 or 1 v 8.5 months for PS2), and RR (odds ratio = 0.61; P< .0001; 43.8% for PS 0 or 1 v32.0% for PS2). The relative benefit and toxicity of experimental versus control treatment and monotherapy versus combination therapy were not different in PS 0 or 1 patients versus PS2 patients. Conclusion In clinical trials, PS2 patients derive similar benefit from superior treatment as patients with PS of 0 to 1 but with an increased risk of toxicities and 12% 60-day mortality. Although current treatment provides benefit, new approaches are required to approach 1-year median survival for PS2 patients. © 2009 by American Society of Clinical Oncology.
Keywords: adult; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; survival rate; retrospective studies; young adult; major clinical study; overall survival; clinical feature; clinical trial; neutropenia; fluorouracil; advanced cancer; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; monotherapy; capecitabine; colorectal cancer; progression free survival; quality of life; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; clinical assessment; cancer mortality; irinotecan; colorectal neoplasms; clinical trials, phase iii as topic; folinic acid; therapy effect; oxaliplatin
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 12
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-01-01
Start Page: 1948
End Page: 1955
Language: English
DOI: 10.1200/jco.2008.20.2879
PUBMED: 19255311
PROVIDER: scopus
PMCID: PMC2669760
DOI/URL:
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: JCOND" - "Source: Scopus"
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  1. Leonard B Saltz
    633 Saltz