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2103 Adjuvant chemotherapy associated with improved relative and overall survival for high risk pT4 stage II colon cancer
Abstracts
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Conclusions: FOLFOXIRI showed similar efficacy and AEs as firstline treatment with FOLFOX/FOLFIRI plus Bev. In conversional therapy, FOLFOXIRI could be recommended as first choice for mCRC, which might avoid the limitation of delaying operation time due to the usage of Bev. No conflict of interest. 2102 POSTER Survival analysis in patients with metastatic colorectal cancer: Correlation with high-cost drug consumption J.C. Camara1 , A.C. Rosero1 , A. Hurtado1 , C.I. Aguayo1 , E. Perez2 , ´ Alcorcon, ´ L. Ruiz-Gimenez1 , C. Jara1 . 1 Hospital Universitario Fundacion ´ Oncology Unit, Alcorcon Madrid, Spain; 2 Hospital Universitario Fundacion ´ Research Unit, Alcorcon Madrid, Spain Alcorcon, Background: Economic crisis has caused a significant decline in health budgets in Spain. In our center, the use of biological drugs (especially bevacizumab) in patients with metastatic colorectal cancer (mCRC) has been reduced by 30%. This study examines the possible relationship between consumption of high cost biologics and survival of mCRC patients (pts.) Material and Methods: We performed a retrospective analysis of two cohorts of mCRC pts: 1. Pts. who started treatment in 2009–2010 (theoretically unaffected by the current financial squeeze) 2. Pts. who started treatment in 2012–2013 (after the implementation of policies to contain pharmaceutical expenditure) A comparison was performed using descriptive statistics for demographic and clinic characteristics in both cohorts. Overall survival in both groups was calculated by Kaplan–Meier, and median survival was compared (log rank test). We also performed a multivariate analysis of prognostic variables (Cox regression). Results: 59 and 41 pts. started treatment in 2009–2010 and 2012–2013 respectively. The main clinical features are summarized in the table.
Number of patients Age: median (range) ECOG: 0 1 2 3 RAS: wild-type mutated unknown mutated unknown Number of metastatic locations
2009–2010
2012–2013
59 66.9 years (37−85)
41 68.8 years (30−85)
21 (35%) 27 (458%) 10 (16.9%) 1 (1.7%)
24 (58.5%) 13 (31.7%) 4 (9.8%) 0 (0%)
25 (42.4%) 23 (39.0%) 11 (18.6%) Median: 2 (1−4)
17 (41.5%) 17 (41.5%) 7 (17%) Median: 2 (1−5)
Signif. p = 0.607 p = 0.132
p = 0.963
p = 0.810
Proportion of patients receiving bevacizumab was significantly lower in the 2012–2013 cohort (50.8% vs 26.8%, p = 0.016). No significant differences were found in the use of anti-EGFR antibodies or chemotherapy in both groups. Median overall survival (OS) for all patients (both cohorts) was 30.8 months (95% CI 25.4–36.3). No significant differences between both groups were found (25.9 vs 30.9 months, p = 0.64), although a non-significant trend toward improved survival was observed in patients treated with bevacizumab in both cohorts (p = 0.051). Only performance status correlated significantly with survival in multivariate analysis (Cox regression). The use of bevacizumab showed a favorable, but not significant, trend in OS (HR 0.62, p = 0.379). Conclusions: In our center, reduced use of bevacizumab in patients with mCRC due to economic circumstances has not resulted in a significant decrease in overall survival. Limitations of this study include its retrospective nature and the limited number of patients analyzed. No conflict of interest. 2103 POSTER Adjuvant chemotherapy associated with improved relative and overall survival for high risk pT4 stage II colon cancer S.R. Verhoeff1 , F.N. Van Erning2 , V.E.P.P. Lemmens3 , J.H.W. De Wilt4 , J.F.M. Pruijt1 . 1 Jeroen Bosch Ziekenhuis, Internal medicine, Den Bosch, Netherlands; 2 Netherlands Comprehensive Cancer Organisation, Research, Eindhoven, Netherlands; 3 Erasmus MC University Medical Centre, Public Health, Rotterdam, Netherlands; 4 Radboud University Nijmegen Medical Centre, Surgery, Nijmegen, Netherlands Background: Adjuvant chemotherapy (CT) should be considered in high risk stage II colon cancer (CC) comprising a pathological T4 tumour (pT4), poor/undifferentiated grade, vascular invasion, emergency surgery and/or
<10 evaluated lymph nodes (LNs). We studied CT-administration and its effect on overall and relative survival for each risk factor (OS/RS). Material and Methods: All patients with high risk stage II CC who underwent resection and were diagnosed in the Netherlands between 2008–2012 were included. After stratification by risk factor(s) (vascular invasion not included), Cox-regression was used to discriminate the independent effect of CT on mortality risk. RS was used to estimate disease-specific survival. Results: 790 of 4940 (16%) patients received CT. Of patients aged 70 years only 6% received CT, vs. 32% of patients aged <70 years (p < 0.0001). Patients more often received CT in case of pT4 (30%) or 2 risk factors (23%). Mortality risk in pT4 patients receiving CT decreased compared to non-recipients (3-year OS 91% vs. 73%, HR 0.43, 95% CI 0.28–0.66), also in patients with 2 risk factors (including pT4-stage) receiving CT compared to non-recipients (3-year OS 83% vs. 64%, HR 0.58, 95% CI 0.43–0.80). Relative excess risk (RER) of dying decreased for patients receiving CT, compared to non-recipients in both pT4-stage (3-year RS 94% vs. 85%, RER 0.36, 95% CI 0.17–0.74) and 2 risk factors (including pT4-stage) (3-year RS 86% vs. 75%, RER 0.52, 95% CI 0.34–0.81). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between CT and RS/OS was observed. Conclusions: In high risk stage II colon cancer, adjuvant chemotherapy in pT4-stage was associated with improved overall and relative survival. Due to the observational nature of the data, interpretation should be cautious. However, refinement of subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. No conflict of interest. 2104 POSTER Derived neutrophil to lymphocyte ratio is not predictive for use of a continuous or intermittent first-line oxaliplatin/fluoropyrimidine combination in patients with advanced colorectal cancer: A post-hoc analysis of the MRC COIN study T. Grenader1 , S. Nash2 , R. Adams3 , R. Kaplan4 , D. Fisher4 , T. Maughan5 , J. Bridgewater1 . 1 University College London, Cancer Institute, London, United Kingdom; 2 University College London, Cancer Research UK & UCL Cancer Trials Centre, London, United Kingdom; 3 Cardiff University School of Medicine Velindre Hospital, Institute of Cancer & Genetics, London, United Kingdom; 4 University College London, MRC Clinical Trials Unit, London, United Kingdom; 5 University of Oxford, CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom. Background: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival. However, a subgroup analysis suggest that patients with normal baseline platelet counts (defined as lower then 400 000 per mL) could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy. The aim of the present correlative analysis was to evaluate whether an alternative biomarker, derived neutrophil to lymphocyte ratio (dNLR), could predict the effect of intermittent versus continuous first-line oxaliplatin and fluoropyrimidine chemotherapy on overall survival (OS) in patients with advanced colorectal cancer. Material and Methods: A post-hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. Lymphocyte count had not been collected at entry to the COIN trial. The dNLR was calculated using a formula that was previously shown to have predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of >3.0. dNLR was then correlated with clinical outcomes including OS, progression-free survival (PFS) and objective response rate (ORR). Survival curves were generated based on dNLR using the Kaplan–Meier method. Comparison between groups was performed using Cox regression. Results: WBC and ANC results were available in 1604 of the 1630 COIN trial arms A and C participants. Of these, 398 (24.8%) were deemed to have a high dNLR. There was a strong inverse association between dNLR level and overall survival. The median survival times in the ITT population were 16.9 months and 10.5 months for patients with low and high dNLR respectively (HR = 1.63; 95% CI, 1.38 to 1.93; P < 0.001). There was no evidence of a differential effect of treatment between the two dNLR groups. In the per protocol population (N = 971), the hazard ratios were 1.09 and 1.36 for the low and high dNLR groups respectively (80% CI, 0.98 to 1.22 and 1.12 to 1.66), (P = 0.21 for interaction between dNLR group and treatment allocation) with no evidence of non-inferiority in either
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Conclusions: FOLFOXIRI showed similar efficacy and AEs as firstline treatment with FOLFOX/FOLFIRI plus Bev. In conversional therapy, FOLFOXIRI could be recommended as first choice for mCRC, which might avoid the limitation of delaying operation time due to the usage of Bev. No conflict of interest. 2102 POSTER Survival analysis in patients with metastatic colorectal cancer: Correlation with high-cost drug consumption J.C. Camara1 , A.C. Rosero1 , A. Hurtado1 , C.I. Aguayo1 , E. Perez2 , ´ Alcorcon, ´ L. Ruiz-Gimenez1 , C. Jara1 . 1 Hospital Universitario Fundacion ´ Oncology Unit, Alcorcon Madrid, Spain; 2 Hospital Universitario Fundacion ´ Research Unit, Alcorcon Madrid, Spain Alcorcon, Background: Economic crisis has caused a significant decline in health budgets in Spain. In our center, the use of biological drugs (especially bevacizumab) in patients with metastatic colorectal cancer (mCRC) has been reduced by 30%. This study examines the possible relationship between consumption of high cost biologics and survival of mCRC patients (pts.) Material and Methods: We performed a retrospective analysis of two cohorts of mCRC pts: 1. Pts. who started treatment in 2009–2010 (theoretically unaffected by the current financial squeeze) 2. Pts. who started treatment in 2012–2013 (after the implementation of policies to contain pharmaceutical expenditure) A comparison was performed using descriptive statistics for demographic and clinic characteristics in both cohorts. Overall survival in both groups was calculated by Kaplan–Meier, and median survival was compared (log rank test). We also performed a multivariate analysis of prognostic variables (Cox regression). Results: 59 and 41 pts. started treatment in 2009–2010 and 2012–2013 respectively. The main clinical features are summarized in the table.
Number of patients Age: median (range) ECOG: 0 1 2 3 RAS: wild-type mutated unknown mutated unknown Number of metastatic locations
2009–2010
2012–2013
59 66.9 years (37−85)
41 68.8 years (30−85)
21 (35%) 27 (458%) 10 (16.9%) 1 (1.7%)
24 (58.5%) 13 (31.7%) 4 (9.8%) 0 (0%)
25 (42.4%) 23 (39.0%) 11 (18.6%) Median: 2 (1−4)
17 (41.5%) 17 (41.5%) 7 (17%) Median: 2 (1−5)
Signif. p = 0.607 p = 0.132
p = 0.963
p = 0.810
Proportion of patients receiving bevacizumab was significantly lower in the 2012–2013 cohort (50.8% vs 26.8%, p = 0.016). No significant differences were found in the use of anti-EGFR antibodies or chemotherapy in both groups. Median overall survival (OS) for all patients (both cohorts) was 30.8 months (95% CI 25.4–36.3). No significant differences between both groups were found (25.9 vs 30.9 months, p = 0.64), although a non-significant trend toward improved survival was observed in patients treated with bevacizumab in both cohorts (p = 0.051). Only performance status correlated significantly with survival in multivariate analysis (Cox regression). The use of bevacizumab showed a favorable, but not significant, trend in OS (HR 0.62, p = 0.379). Conclusions: In our center, reduced use of bevacizumab in patients with mCRC due to economic circumstances has not resulted in a significant decrease in overall survival. Limitations of this study include its retrospective nature and the limited number of patients analyzed. No conflict of interest. 2103 POSTER Adjuvant chemotherapy associated with improved relative and overall survival for high risk pT4 stage II colon cancer S.R. Verhoeff1 , F.N. Van Erning2 , V.E.P.P. Lemmens3 , J.H.W. De Wilt4 , J.F.M. Pruijt1 . 1 Jeroen Bosch Ziekenhuis, Internal medicine, Den Bosch, Netherlands; 2 Netherlands Comprehensive Cancer Organisation, Research, Eindhoven, Netherlands; 3 Erasmus MC University Medical Centre, Public Health, Rotterdam, Netherlands; 4 Radboud University Nijmegen Medical Centre, Surgery, Nijmegen, Netherlands Background: Adjuvant chemotherapy (CT) should be considered in high risk stage II colon cancer (CC) comprising a pathological T4 tumour (pT4), poor/undifferentiated grade, vascular invasion, emergency surgery and/or
<10 evaluated lymph nodes (LNs). We studied CT-administration and its effect on overall and relative survival for each risk factor (OS/RS). Material and Methods: All patients with high risk stage II CC who underwent resection and were diagnosed in the Netherlands between 2008–2012 were included. After stratification by risk factor(s) (vascular invasion not included), Cox-regression was used to discriminate the independent effect of CT on mortality risk. RS was used to estimate disease-specific survival. Results: 790 of 4940 (16%) patients received CT. Of patients aged 70 years only 6% received CT, vs. 32% of patients aged <70 years (p < 0.0001). Patients more often received CT in case of pT4 (30%) or 2 risk factors (23%). Mortality risk in pT4 patients receiving CT decreased compared to non-recipients (3-year OS 91% vs. 73%, HR 0.43, 95% CI 0.28–0.66), also in patients with 2 risk factors (including pT4-stage) receiving CT compared to non-recipients (3-year OS 83% vs. 64%, HR 0.58, 95% CI 0.43–0.80). Relative excess risk (RER) of dying decreased for patients receiving CT, compared to non-recipients in both pT4-stage (3-year RS 94% vs. 85%, RER 0.36, 95% CI 0.17–0.74) and 2 risk factors (including pT4-stage) (3-year RS 86% vs. 75%, RER 0.52, 95% CI 0.34–0.81). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between CT and RS/OS was observed. Conclusions: In high risk stage II colon cancer, adjuvant chemotherapy in pT4-stage was associated with improved overall and relative survival. Due to the observational nature of the data, interpretation should be cautious. However, refinement of subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. No conflict of interest. 2104 POSTER Derived neutrophil to lymphocyte ratio is not predictive for use of a continuous or intermittent first-line oxaliplatin/fluoropyrimidine combination in patients with advanced colorectal cancer: A post-hoc analysis of the MRC COIN study T. Grenader1 , S. Nash2 , R. Adams3 , R. Kaplan4 , D. Fisher4 , T. Maughan5 , J. Bridgewater1 . 1 University College London, Cancer Institute, London, United Kingdom; 2 University College London, Cancer Research UK & UCL Cancer Trials Centre, London, United Kingdom; 3 Cardiff University School of Medicine Velindre Hospital, Institute of Cancer & Genetics, London, United Kingdom; 4 University College London, MRC Clinical Trials Unit, London, United Kingdom; 5 University of Oxford, CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom. Background: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival. However, a subgroup analysis suggest that patients with normal baseline platelet counts (defined as lower then 400 000 per mL) could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy. The aim of the present correlative analysis was to evaluate whether an alternative biomarker, derived neutrophil to lymphocyte ratio (dNLR), could predict the effect of intermittent versus continuous first-line oxaliplatin and fluoropyrimidine chemotherapy on overall survival (OS) in patients with advanced colorectal cancer. Material and Methods: A post-hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. Lymphocyte count had not been collected at entry to the COIN trial. The dNLR was calculated using a formula that was previously shown to have predictive power in cancer patients: dNLR=ANC/(WBC-ANC). A high dNLR was defined using a cut-off value of >3.0. dNLR was then correlated with clinical outcomes including OS, progression-free survival (PFS) and objective response rate (ORR). Survival curves were generated based on dNLR using the Kaplan–Meier method. Comparison between groups was performed using Cox regression. Results: WBC and ANC results were available in 1604 of the 1630 COIN trial arms A and C participants. Of these, 398 (24.8%) were deemed to have a high dNLR. There was a strong inverse association between dNLR level and overall survival. The median survival times in the ITT population were 16.9 months and 10.5 months for patients with low and high dNLR respectively (HR = 1.63; 95% CI, 1.38 to 1.93; P < 0.001). There was no evidence of a differential effect of treatment between the two dNLR groups. In the per protocol population (N = 971), the hazard ratios were 1.09 and 1.36 for the low and high dNLR groups respectively (80% CI, 0.98 to 1.22 and 1.12 to 1.66), (P = 0.21 for interaction between dNLR group and treatment allocation) with no evidence of non-inferiority in either