Abstract 3554
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.
Resources from the same session
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract
1694 - Pembrolizumab (pembro) Plus mFOLFOX or FOLFIRI in Patients With Metastatic Colorectal Cancer (mCRC): KEYNOTE-651 Cohorts B and D
Presenter: Richard Kim
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract