3554 - Patient characteristics associated with poor performance status, ECOG 2-3, and effect on survival in 1086 Finnish metastatic colorectal cancers (mCRC) nationwide (prospective RAXO study)

Background

ECOG 2-3 patients are poorly represented in prospective studies (only 7% in Sorbye et al, Ann Oncol 2007) and efficacy outcomes are poor. Natural course of mCRC and metastasectomies were the primary endpoints of this prospective Finnish nationwide study initiated in 2011.

Methods

1086 mCRCs referred for oncological treatments at all 21 oncology units (40% of eligible mCRCs in Finland) were included. Prognostic and predictive factors, resectability, treatment history and outcome measures were assessed.

Results

Baseline ECOG was 0 in 295 (27%), 1 in 600 (55%) and 2-3 in 191 (18%). Strongest baseline patient characteristics in multivariable logistic regression models (n = 851) for ECOG 2-3 status were: age >70 (odds ratio 3.00), BMI <20 (2.26), >3 comorbidities (2.61), >3 regular drugs (1.67), >2 symptoms at mCRC diagnosis (3.05), abnormal physical exam (2.22), bone metastases (3.37), BRAF mutation (2.44), neutrophil-to-lymphocyte ratio >3.00 (2.75), alkaline phosphatase ALP >300 (3.08), leukocytes >10 (1.88), haemoglobin <11 (1.70) and in univariable analysis also, daily drinking (2.55), smoking (1.98), primary in-situ (2.38), >3 metastatic sites (1.92), synchronous mets (1.77); suprarenal (2.87), liver (1.53) and lymph node metastases (1.44); neutrophils >6.7 (4.54), platelets >400 (1.73), CRP >10 (3.37), albumin <30 (4.70), CEA >5 (2.51) and Ca19-9 >25 (1.61). Sex, second cancers, sidedness, RAS status or MSI-H were not associated with ECOG 2-3 status. In ECOG 0 / 1 / 2-3 median overall survival (OS) was 46.0 / 29.1 / 13.2 months and progression free survival (PFS) 18.6 / 12.5 / 7.0 months, respectively. Cox proportional hazards models for OS and PFS suggested that baseline ECOG 2-3, bone metastases, BRAF mutation, >3 metastatic sites, elevated ALP or leukocytes were the strongest predictors of poor OS and PFS.

Conclusions

Poor performance status is characterized by comorbidities, drinking and smoking; cancer-related symptoms, tumour burden, laboratory alterations and inflammatory activity. ECOG 2-3 is one of the strongest prognostic factors, and OS is shortened by > 12 months per ECOG class and PFS by 6 months.

Clinical trial identification

NCT01531621.

Editorial acknowledgement

Legal entity responsible for the study

The authors of the RAXO-study group.

Funding

Finska Läkaresällskapet, The Finnish Cancer Foundation, the Competitive State Research Financing of the Expert Responsibility Area of Tampere and Helsinki University Hospitals, Amgen - unrestricted grant, Eli Lilly, Merck, Roche, Sanofi and Servier - unrestricted grant.

Disclosure

P.J. Österlund: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nordic Drugs; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Baxalta/Servier; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Travel / Accommodation / Expenses: AbbVie; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Pierre Fabre. T. Salminen: Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier; Speaker Bureau / Expert testimony: Novartis. A. Algars: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Servier; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Varian; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly. L. Soveri: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Sanofi. R. Ristamäki: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self): Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. R.S. Kallio: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier. A. Lamminmäki: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier; Travel / Accommodation / Expenses: Kyowa Kirin; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: BMS. T. Poussa: Honoraria (institution): Boehringer Ingelheim. E. Lantto: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. A. Ovissi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. A. Nordin: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Lilly; Honoraria (institution): Merck; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Servier. P. Nyandoto: Advisory / Consultancy: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly. J.T. Kononen: Advisory / Consultancy: Amgen; Research grant / Funding (self): Merck; Advisory / Consultancy: Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Honoraria (self): Celgene; Advisory / Consultancy: BMS. L.J. Aroviita: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. A. Jekunen: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Ibsen; Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Takeda. M. Murashev: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. R. Lindvall-Andersson: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. H. Isoniemi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Servier. All other authors have declared no conflicts of interest.