Validation of the Immunoscore prognostic value in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3513-3513 ◽  
Author(s):  
Franck Pages ◽  
Thierry Andre ◽  
Julien Taieb ◽  
Dewi Vernerey ◽  
Julie Henriques ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cohort Study ◽  
Multivariable Analysis ◽  
Digital Pathology ◽  
Disease Free Survival ◽  
Continuous Variable ◽  
Primary Objective ◽  
Stage Iii ◽  
Cox Models ◽  
N Stage

3513 Background: The Immunoscore (IS), which has been shown to prognostically classify Stage I-III colon cancer (CC) patients, was assessed in the IDEA France cohort study evaluating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in Stage III CC patients. Methods: Densities of CD3+ and cytotoxic CD8+ T cells in the tumor and invasive margin of each patient were quantified by digital pathology and converted to IS using pre-defined published cut-off. The performance of IS to predict disease-free survival (DFS) was assessed in the modified intention-to-treat population, in each study arm, and was adjusted with relevant clinical features in multivariable Cox models. Harrell’s C-statistics was used to investigate the IS performance. Results: 1322 patients were included; 82 were excluded due to pre-analytical non-conformity. IS was successfully analyzed in 1062 (85.6%) eligible patients. In a 2-category IS analysis, Low and (Int+High) IS were observed in n=599 (43.6%) and n=463 (56.4%) patients, respectively. IS was significantly correlated with T stage, T/N stage (T1-3 and N1 versus T4 and/or N2), and microsatellite instability status. The study met its primary objective of validating that Low IS identifies patients with higher-risk of relapse or death [HR=1.54; 95%CI 1.24-1.93, p=0.0001]. The 3-year DFS rates were 66.80% [95%CI 62.23-70.95] and 77.14% [95%CI 73.50-80.35] for Low IS and (Int+High) IS, respectively. In multivariable analysis, IS remained independently associated with DFS (p<0.0012) when combined with T/N stage. The addition of IS to the T/N stage significantly improved the model discrimination capacity [bootstrap C index mean difference, 0.022; 95%CI 0.005-0.04]. In addition, IS in 3 categories (Low, Int, High) and as a continuous variable were also both significantly associated with DFS (all p<0.001). In univariable analysis, IS was also associated with DFS in 6 months arm (p<0.0001); a similar trend was observed in 3 months arm (p=0.09). Conclusions: IS was confirmed as a prognostic factor of DFS in Stage III CC patients in the prospective IDEA France cohort study. Clinical trial information: NCT03422601.

scholarly journals Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer

2020 ◽  
Vol 38 (31) ◽  
pp. 3638-3651 ◽  
Author(s):  
Bernhard Mlecnik ◽  
Carlo Bifulco ◽  
Gabriela Bindea ◽  
Florence Marliot ◽  
Alessandro Lugli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariable Analysis ◽  
Digital Pathology ◽  
Disease Free Survival ◽  
Cancer Control ◽  
Recurrence Risk ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Response To Chemotherapy ◽  
Immunotherapy Of Cancer

PURPOSE The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR). METHODS An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy. RESULTS Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient’s sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low], 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group ( P > .12). CONCLUSION This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.

scholarly journals Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage III Colon Cancer

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Frank A Sinicrope ◽  
Qian Shi ◽  
Fabienne Hermitte ◽  
Tyler J Zemla ◽  
Bernhard Mlecnik ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Statistical Tests ◽  
Disease Free Survival ◽  
Braf V600e ◽  
Stage Iii ◽  
Survival Prediction ◽  
Cox Models ◽  
Stage Iii Colon Cancer ◽  
T Stage ◽  
Molecular Features

Abstract Background The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. Methods Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, and Immunoscore (CD3+, CD8+ T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided. Results Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.19 to 2.60; P = .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; P = .005), BRAF V600E (HR = 1.74, 95% CI = 1.26 to 2.40; P &lt; .001), mutant KRAS (HR = 1.66, 95% CI = 1.08 to 2.55; P = .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; P = .001) (all P &lt; .02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both Ps&lt; .0001). After number of +LNs, T stage, and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T1–3 N1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years. Conclusions The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.

Prognostic value of tumor deposits for disease free survival in patients with stage III colon cancer: A post hoc analysis of IDEA France phase III trial (PRODIGE-GERCOR).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3519-3519
Author(s):  
Jean Francois Delattre ◽  
Romain Cohen ◽  
Julie Henriques ◽  
Antoine Falcoz ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cox Model ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Tnm Staging ◽  
Phase Iii ◽  
Stage Iii ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

3519 Background: Tumor deposits (TDs) are isolated tumor foci in the pericolic, perirectal or mesocolic fat without residual lymph node (LN) tissue. TDs seem to impact the prognosis of stage III colon cancer (CC) patients (pts) but are only considered in TNM staging in the absence of LN metastases (LNM). We aimed at evaluating the prognosis value for disease free survival (DFS)of TDs in International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France phase III study (NCT00958737) that compared 3 versus 6 months of adjuvant FOLFOX or CAPOX for stage III CC pts. Methods: All pathological reports of pts included in IDEA France trial were retrospectively analyzed. DFS according to the presence or absence of TDs was evaluated using Kaplan-Meier estimator. Multivariable Cox model analysis was performed to evaluate the association between TDs and DFS. This analysis did not included immunohistochemical biomarkers. Results: Among the 2022 pts included in IDEA France study, 1942 (96%) were analyzed. 80 pts were excluded: no pathological report (n = 68), pts without treatment (n = 12). TDs were found in 184 pts (9.47%), of whom 74 with N1a/b (40%), 55 with N1c (30%) and 55 with N2 LN stage (30%). All characteristics were similar according to the presence of TDs, except for tumor/node (TN) stage (T4 and/or N2 are more frequent in pts with TDs; p = .0046). The 3-year DFS rates were 65.59% [95% confidence interval (95%CI) 58.04-72.12] and 74.71% [95%CI 72.57-76.71] for pts with and without TDs, respectively (p = 0.0079). In multivariable analysis, TDs were associated with higher risk of recurrence or death (hazard ratio (HR) = 1.36, 95%CI 1.05-1.75, p = .0201), as well as T4 and/or N2 (HR = 2.21, 95%CI 1.03-1.59, p < .001), 3 months of adjuvant treatment (HR = 1.29, 95%CI 1.09-1.52, p = .0029), obstruction (HR = 1.28, 95%CI 1.03-1.59, p = .0233) and male (HR = 1.24, 95%CI 1.04-1.46, p = .0151). Adding TDs count to the LNM count, 35 out of 1454 N1a/b/c CC pts (2.4%) were reclassified as N2 and experienced worse 3 years DFS than confirmed N1 CC pts (p = .0151). Conclusions: TD is an independent and valuable prognostic factor for DFSin stage III CC pts and should be considered whatever the LNM status.

Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with mFOLFOX6 (three versus six months) in the prospective IDEA France cohort study (PRODIGE-GERCOR).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 10-10
Author(s):  
Franck Pages ◽  
Thierry Andre ◽  
Julien Taieb ◽  
Dewi Vernerey ◽  
Julie Henriques ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cohort Study ◽  
High Risk ◽  
Cancer Patients ◽  
Predictive Value ◽  
External Validation ◽  
Disease Free Survival ◽  
Low Risk ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

10 Background: In stage III colon cancer patients treated with CAPOX, 3 months of therapy was as effective as 6 months. It was not the case for those receiving mFOLFOX6. We assessed the prognostic and predictive value of the Immunoscore (IS) in the mFOLFOX6 subgroup (90% of patients enrolled) of the IDEA France cohort study. Methods: 1200 patients randomly assigned to 3 months (n = 593) or 6 months (n = 607) of mFOLFOX6, with available tumor sample, were included. Densities of CD3+ and cytotoxic CD8+ T-cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS using the pre-defined cut-off. The IS performance to predict disease-free survival (DFS) was assessed in each arm and adjusted in multivariate Cox models. Results: In a two-category IS analysis, Low and (Int+High) IS were observed in 423 (43.5%) and 550 (56.5%) patients, respectively. Low IS identified patients with higher-risk of relapse or death (HR = 1.60; 95% CI 1.27-2.01, P < 0.0001). The 3-year DFS was 66.34% (95% CI 61.54-70.69) and 77.66% (95% CI 73.86-80.97) for Low and (Int+High) IS, respectively. In multivariate analysis, IS remained independently associated with DFS (P = 0.0007) when combined with T/N stage. A statistically significant interaction was observed for the IS predictive value for treatment duration (3 vs 6 months) in term of DFS in the whole population (P = 0.0566) and TN subgroups (Low-risk T1-3, N1 vs High-risk T4 and/or N2; P = 0.0015). The 3-year DFS of patients with (Int+High) IS in the 3-month arm was 71.5% (95% CI 65.7-76.6) versus 83.8% (95% CI, 78.8-87.8) in the 6-month arm (HR = 0.528; 95% CI 0.372-0.750; log-rank P = 0.0004); the benefit retained in low-risk and high-risk patients (all P≤0.010). 6-month mFOLFOX6 showed no significant benefit for patients with Low IS (HR = 0.836, log-rank P = 0.269). Conclusions: The IS prognostic value in patients treated with mFOLFOX6 was confirmed. Its predictive value for benefit of longer duration treatment, despite a strong statistical signal, needs to be confirmed in an external validation cohort. Clinical trial information: NCT03422601.

scholarly journals A Novel Prognostic Model Incorporating Carcinoembryonic Antigen in 3-Week or Longer Postoperative Period for Stage III Colon Cancer: A Multicenter Retrospective Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Jin Fan ◽  
Yanlong Liu ◽  
Xin Cai ◽  
Jingwen Wang ◽  
Rui Guo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Carcinoembryonic Antigen ◽  
Prognostic Model ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Net Reclassification Improvement ◽  
Model Combining ◽  
N Stage

BackgroundThe prognostic stratification of colon cancer using only the tumor-node-metastasis (TNM) stage has some limitations. We sought to increase the accuracy of stratifying patients with stage III colon cancer by constructing a prognostic model combining carcinoembryonic antigen (CEA) with TNM.MethodsWe retrospectively analyzed the data generated from stage III colon cancer patients who had early postoperative CEA measurement from 21 to 100 days after surgery from 2006 to 2017. CEA value was processed using restricted cubic splines (RCS) method. The prognostic model was developed using cox proportional hazards regression.ResultsThe time later than 20 days after surgery was optimal for measuring CEA, which was determined by comparing the prognostic value for preoperative and postoperative CEA (N = 2,049), and by evaluating the relationship between the hazard ratio (HR) and postoperative CEA measuring time. Postoperative CEA, T stage and N stage were selected into the final model, and the mean integrated-AUC (iAUC) was 0.78 with 1,000 × bootstrap resampling, which was higher than the model using only T and N stages (TN model; mean iAUC, 0.66). The net reclassification improvement (NRI) was 15% when compared with TN model. Patients could be divided into high and low risk groups by the model, and 3-year disease-free survival (DFS) were 53.7% and 87.0%, respectively (HR, 4.30; 95% CI, 2.65 to 6.96; P &lt; 0.001). Similar results were found in the validation set.ConclusionsStage III colon cancer could be stratified more accurately using the new prognostic model combining postoperative CEA with T and N stage.

scholarly journals Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR)

2020 ◽  
Vol 38 (15) ◽  
pp. 1702-1710
Author(s):  
Jean-François Delattre ◽  
Romain Cohen ◽  
Julie Henriques ◽  
Antoine Falcoz ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Free Survival ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Disease Free

PURPOSE Tumor deposits (TDs) seem to affect the prognosis of patients with colon cancer (CC). In the seventh edition of the American Joint Committee on Cancer TNM staging system for CC, the presence of TDs is only considered in the absence of lymph node metastases (LNMs). In the era of personalized duration of histopathologic criteria-based adjuvant therapy, this could potentially lead to a decrease in the prognostic prediction accuracy. PATIENTS AND METHODS A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737 ) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.

Randomized Phase III Trial Comparing Biweekly Infusional Fluorouracil/Leucovorin Alone or With Irinotecan in the Adjuvant Treatment of Stage III Colon Cancer: PETACC-3

2009 ◽  
Vol 27 (19) ◽  
pp. 3117-3125 ◽  
Author(s):  
Eric Van Cutsem ◽  
Roberto Labianca ◽  
György Bodoky ◽  
Carlo Barone ◽  
Enrique Aranda ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Stage Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
Stage Iii Colon Cancer

PurposeThe primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer.Patients and MethodsAfter curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m2as a 2-hour infusion, followed by FU; as a 400 mg/m2bolus and then a 600 mg/m2continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m2as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan.ResultsThe principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia.ConclusionIrinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.

Histopathological Predictors of Recurrence in Stage III Colon Cancer: Reappraisal of Tumor Deposits and Tumor Budding Using AJCC8 Criteria

2018 ◽  
Vol 27 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Michael A. Landau ◽  
Benjamin Zhu ◽  
Frances N. Akwuole ◽  
Reetesh K. Pai
Keyword(s):  
Colon Cancer ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Stage Iii ◽  
Tumor Budding ◽  
Stage Iii Colon Cancer ◽  
Predictors Of Recurrence ◽  
Increased Risk ◽  
Cancer Tumor

Patients with stage III colonic adenocarcinoma have a spectrum of risk for recurrent disease, and histopathological variables that predict recurrence can help stratify patients into prognostic groups. To identify histopathological predictors of recurrence, we investigated the effect of implementation of the eighth edition of the American Joint Committee on Cancer (AJCC8) staging system definition of tumor deposits and International Tumor Budding Consensus Conference (ITBCC) criteria for tumor budding compared with other known prognostic variables in 256 resected colonic adenocarcinomas, including 150 stage III and 106 stage II tumors. In stage III colon cancer, tumor deposits and high tumor budding were the only independent histological variables that predicted disease recurrence. In a multivariable analysis in stage III colon cancer, tumor deposits and high tumor budding were associated with a 2.2- and 1.5-fold increased risk of developing disease recurrence, respectively (95% CI = 1.1-4,2, P = .02, and 95% CI = 1.1-2.1, P = .01, respectively). The negative prognostic effect of tumor deposits was most pronounced in patients with stage IIIB disease in which tumor deposits were associated with a 3.2-fold increased risk of disease recurrence (95% CI = 1.4-7.1; P = .005). Within the N1 cohort, patients with tumor deposits without concurrent positive lymph nodes (N1c) had a significantly decreased disease-free survival compared with patients with N0 tumors ( P < .001) and patients with N1a/b tumors ( P = .02). As independent risk factors for recurrence, tumor deposits and high tumor budding are important histopathological variables and should be included as a part of a routine comprehensive pathological risk assessment in stage III colon cancer.

scholarly journals Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials

2020 ◽  
pp. JCO.20.01600
Author(s):  
Romain Cohen ◽  
Julien Taieb ◽  
Jack Fiskum ◽  
Greg Yothers ◽  
Richard Goldberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Prognostic Value ◽  
Randomized Clinical Trials ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Cox Models ◽  
Stage Iii Colon Cancer ◽  
Similar Survival

PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.

Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 710-710
Author(s):  
Jonathan M. Loree ◽  
Aaron Sha ◽  
Maryam Soleimani ◽  
Maria Yi Ho ◽  
Hagen F. Kennecke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Dose Intensity ◽  
Phase Iii ◽  
Stage Iii ◽  
Rank Test ◽  
Cox Models ◽  
Stage Iii Colon Cancer ◽  
T Stage ◽  
N Stage

710 Background: CAPOX and FOLFOX are used interchangeably in the adjuvant treatment of colon cancer despite the lack of comparative phase III trials.We aimed to compare toxicities, relative dose intensity (RDI), disease free (DFS) and overall survival (OS) of these regimens in the real world. Methods: We identified consecutively treated patients (pts) with stage III colon cancer at two centers who received either CAPOX or mFOLFOX6 when either option was accessible to pts. RDI was defined as total dose received divided by the total intended dose if all cycles had been delivered. Dose limiting toxicities (DLTs) were toxicities that resulted in a dose reduction of an agent. Survival was compared with the log-rank test and Cox models that adjusted for age, gender, ECOG, T-stage, and N-stage. Results: Of 394 pts, 61.7% received FOLFOX. Age, gender, ECOG, T-stage, N-stage, and time between surgery and start of therapy did not differ between groups. However, RDI and toxicity profiles differed between treatment groups (see Table). With a median follow up of 45 months, there was no difference in OS (HR 0.73, 95%CI 0.45-1.22; P= 0.24); however, CAPOX was associated with a more favorable DFS (HR 0.61, 95% CI 0.40-0.93; P= 0.022). In multivariate analysis, treatment with CAPOX showed trends towards improved OS (HR 0.61, 95% CI 0.34-1.07; P= 0.086). A significant association with improved DFS (HR 0.53, 95% CI 0.33-0.87; P= 0.012) persisted. Exploratory analysis comparing outcomes stratified by the presence of any DLT, neutropenia, thrombocytopenia, and neuropathy failed to show an association with either OS or DFS. (See table.) Conclusions: Our findings suggest that the use of adjuvant CAPOX is associated with an improved DFS despite greater toxicity and lower RDI. Patient selection, the higher starting dose of oxaliplatin in CAPOX, or the metronomic nature of capecitabine may be contributing to improved efficacy of CAPOX. [Table: see text]

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