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Meta-Analysis
. 2009 Apr 20;27(12):1948-55.
doi: 10.1200/JCO.2008.20.2879. Epub 2009 Mar 2.

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

Daniel J Sargent  1 , Claus Henning Köhne, Hanna Kelly Sanoff, Brian M Bot, Matthew T Seymour, Aimery de Gramont, Ranier Porschen, Leonard B Saltz, Philippe Rougier, Christopher Tournigand, Jean-Yves Douillard, Richard J Stephens, Axel Grothey, Richard M Goldberg
Affiliations
Meta-Analysis

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

Daniel J Sargent et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2009 Jul 10;27(20):3410-1

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 > or = 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 > or = 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 v 32.0% 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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
(A) Progression-free survival and (B) overall survival by performance status (PS), regardless of treatment. HR, hazard ratio.
Fig 2.
Fig 2.
Forest plot of study-specific progression-free survival (PFS) hazard ratios (HR) by performance status (PS). FU, fluorouracil; LV, leucovorin; FOLFIRI, infusional fluorouracil, leucovorin, and irinotecan; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; IFL, irinotecan, fluorouracil, and leucovorin; IROX, irinotecan and oxaliplatin.
Fig 3.
Fig 3.
Forest plot of study-specific overall survival hazard ratios (HR) by performance status (PS). FU, fluorouracil; LV, leucovorin; FOLFIRI, infusional fluorouracil, leucovorin, and irinotecan; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; IFL, irinotecan, fluorouracil, and leucovorin; IROX, irinotecan and oxaliplatin; CPT, irinotecan.
Fig 4.
Fig 4.
Forest plot of study-specific response rate odds ratios (OR) by performance status (PS). FU, fluorouracil; LV, leucovorin; FOLFIRI, infusional fluorouracil, leucovorin, and irinotecan; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; IFL, irinotecan, fluorouracil, and leucovorin; IROX, irinotecan and oxaliplatin.
See this image and copyright information in PMC

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