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The Immunoscore (IS), which prognostically classifies stage I–III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24–1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23–70.94) for IS Low and 77.14% (95% CI 73.50–80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37–0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. NCT03422601 ; EudraCT Number: 2009-010384-16. • This study provides evidence for the feasibility and reproducibility of the Immunoscore (IS) test. • The IS prognostic value for disease-free survival (DFS) is demonstrated in stage III patients treated with oxaliplatin-based chemotherapy. • A predictive value of the IS (Int + High) for DFS benefit of longer duration of mFOLFOX6 treatment is observed. • Patients with low- and high-risk stage having IS Int + High significantly benefit from 6 months' mFOLFOX6 versus IS Low. [ABSTRACT FROM AUTHOR]

Background Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. Patients and methods Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). Results 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75–91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. Conclusion Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL. [ABSTRACT FROM AUTHOR]

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consideras inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progressionfree survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria. [ABSTRACT FROM AUTHOR]

Backgroud: The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point. Patienst and methods: Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen. Results: Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3-4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44). Conclusion: Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II-III rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative. Patients and methods: In this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m2) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m2) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m2). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong’s prognostic score. The primary end point was 2-year disease-free survival (DFS). Results: A total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7–FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7–FOLFIRI. [ABSTRACT FROM AUTHOR]