Originally published as JCO Early Release 10.1200/JCO.2008.20.2879 on March 2 2009

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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

From the Mayo Clinic, Rochester, MN; University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York, NY; Klinikum Oldenburg, Oldenburg; Klinikum Bremen, Bremen, Germany; Cancer Research Center UK Clinical Centre, Leeds; Medical Research Council, London, United Kingdom; Hopital Saint Antoine, Paris; Hopital Ambroise Pare, Boulogne; and Center R. Gauducheau, St Herblain, France.

Corresponding author: Daniel Sargent, PhD, Mayo Clinic, 200 1st St SW, Rochester, MN 55905; e-mail: sargent.daniel{at}mayo.edu.

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 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.

Supported by North Central Cancer Treatment Group Grant No. CA25224 from the National Cancer Institute.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

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

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