Months Of Oxaliplatin-based Adjuvant Chemotherapy Research Articles

Impact of the IDEA Collaboration Study on Real-World Practice Patterns of Adjuvant Chemotherapy in Patients With Stage III Colon Cancer: A Population-Based Study.

The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration showed no significant clinical difference in outcomes in patients with stage III colon cancer (CC) treated with 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy (O-ACT). We aimed to assess change in real-world practice patterns before and after publication of the IDEA study. This retrospective cohort study included patients age ≥18 years with stage III CC diagnosed between January 1, 2012, and December 31, 2020. Eligible patients received >1 dose of ACT between March 20, 2012, and May 10, 2021 inclusive. They were categorized into pre-IDEA (diagnosed before March 31, 2018) and post-IDEA (diagnosed on or after April 1, 2018) groups. The primary outcome was the median duration and type of ACT and factors associated with a shorter duration. Secondary outcomes were 2-year overall survival (OS) and cancer-specific survival (CSS). In total, 740 patients were included (median age, 64 years, range, 27-90; 52.7% male). 48.8% had pT4 and/or pN2 disease. 77% received O-ACT. In the post-IDEA era, capecitabine plus oxaliplatin (CAPOX) ACT use increased (22.8%-50.7%, P < .001), and median duration of treatment was significantly shorter (2.7 v 4.8 months, P < .001). Factors associated with shorter O-ACT duration included diagnosis in the post-IDEA era (odds ratio, 2.08, P = .002), absence of pT4 and/or pN2 disease (hazard ratio [HR], 1.71, P = .01), and receipt of CAPOX (HR, 2.58, P < .001). Two-year OS and CSS were comparable between pre- and post-IDEA eras (OS 95% v 94%; CSS 96% v 96%). Our study shows that the results of the IDEA trial have been largely adopted in clinical practice with shorter duration of ACT in low-risk stage III CC.

Impact of the IDEA collaboration study on practice patterns of adjuvant chemotherapy in patients with stage III colon cancer: A population-based study.

533 Background: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration showed no significant clinical difference in outcomes in patients with stage III colon cancer treated with 3 months versus 6 months of oxaliplatin-based adjuvant chemotherapy (O-ACT). We aimed to assess the change in practice patterns of ACT before and after publication of the IDEA study. Methods: This was a retrospective, population-based, cohort study of patients ≥ 18 years of age diagnosed with stage III colon cancer between January 1, 2012 and December 31, 2021 in Alberta, Canada. Eligible patients received &gt;1 dose of ACT. Patients were divided into two groups; pre-IDEA (diagnosed prior to March 31, 2018) and post-IDEA (diagnosed on or after April 1, 2018). Treatment duration was categorized as short (&lt;4.5 months) and long (≥4.5 months). The primary outcome was the median duration and type of ACT and factors associated with a shorter duration of ACT. Two-year overall survival (OS) and cancer-specific survival (CSS) were secondary outcomes. Results: We identified a total of 735 patients. Median age at diagnosis was 64 years (range 27-90 years) and 52.8% (N=388) were male. 48.8% (N=359) patients had had pT4 and/or pN2 disease. 78% (N=572) received O-ACT. In the post-IDEA era, the use of capecitabine plus oxaliplatin (CAPOX) ACT increased (23.0% to 50.9%, p&lt;0.001) and median duration of O-ACT was significantly shorter (2.7 vs 4.8 months, p&lt;0.001). On multivariable logistic regression, factors associated with shorter duration of ACT included treatment in the post-IDEA era (odds ratio [OR] 1.85, p=0.007), no pT4 and/or pN2 disease (OR 1.6, p=0.02), and receipt of CAPOX ACT (OR 2.7, p&lt;0.001). Characteristics not significantly associated with ACT duration included age, sex, residence rurality, neighborhood income, and comorbidity index. The 2-year OS and CSS was similar in the pre-IDEA and post-IDEA eras (OS 95% vs 93%, p=0.29; CSS 96% vs 96%, p=0.30). Neither time era or treatment duration were independently associated with OS or CSS in multivariable models. Conclusions: Our study is one of the first that shows that the results of the IDEA trial have been largely adopted in clinical practice with shorter duration of ACT and increased use of CAPOX ACT in low-risk stage III colon cancer using population-based data.

Real-world adjuvant chemotherapy treatment patterns and outcomes over time for resected stage II and III colorectal cancer.

The administration of adjuvant chemotherapy (AC) to colorectal cancer (CRC) patients in Australia and impact of recent trial data has not been well reported. We aim to evaluate temporal trends in AC treatment and outcomes in real-world Australian patients. CRC patients were analyzed from 13 hospitals, stratified by stage (II or III) and three 5-year time periods (A: 2005-2009, B: 2010-2014, C: 2015-2019). Stage III was further stratified as pre- and post publication of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration (March 2018). AC prescription, time-to-recurrence (TTR), and overall survival (OS) was compared across the time periods. Of 3977 identified patients, 1148 (stage II: 640, stage III: 508), 1525 (856 vs. 669), and 1304 (669 vs. 635) were diagnosed in Period A, B, and C, respectively. Fewer patients in Period C received AC compared to Period B in stage II (10% vs. 15%, p <.01) and III (70% vs. 79%, p <.01). Post-IDEA, the proportion of patients receiving ≤3 months of oxaliplatin-based AC increased (45% vs. 13%, p <.01). The proportion of patients who remained recurrence free at 3 years was similar between time periods in stage II (A: 89% vs. B: 88% vs. C: 90%, p = .53) and stage III (72% vs. 76% vs. 72%, p = .08). OS significantly improved for stage II (80%-85%, p = .04) and stage III (69%-77%, <.01) from period A to B. AC use has moderately decreased over time with no impact on recurrence rates. Improved survival in more recent years despite similar recurrence rates may be related to improved baseline staging, better postrecurrence treatment, and reduced noncancer-related mortality.

Translation of IDEA trial results into clinical practice: Analysis of the implementation of a new guideline for colon cancer.

The IDEA trial showed no clinical relevant differences in efficacy between 3 and 6 months of oxaliplatin‐based adjuvant chemotherapy (ACT) in colon cancer (CC), while toxicity was substantially lower in the 3 months regimen. Therefore, in 2017 the Dutch colorectal cancer guideline was revised and currently recommends 3 months of oxaliplatin‐based ACT. Furthermore, the definition of high‐risk stage II CC was restricted to pT4 tumors. We analyzed changes in ACT between 2015 and 2019. From the Netherlands Cancer Registry all 16 721 patients ≥18 years with resected high‐risk stage II and stage III CC during 2015 to 2019 were selected. Differences in patient and treatment characteristics were analyzed per calendar year according to stage and age. Mean duration of oxaliplatin‐based ACT decreased from 18.6 (±8.0) to 9.5 (±3.8) weeks between 2015 and 2019. In patients receiving ACT (n = 8170), the proportion treated with oxaliplatin increased from 74% to 83%. The proportion of patients receiving ACT was stable, 61% to 69% in stage III and 26% to 29% in pT4 stage II. ACT in previous high‐risk pT3N0 disease decreased from 15% to 3%. Use of oxaliplatin increased from 27% to 49% in patients aged ≥75 years. The revised guideline was rapidly implemented and led to an increase in oxaliplatin‐based ACT in the elderly and increased guideline‐adherence in high‐risk stage II CC.

Prognostic impact of early treatment discontinuation and early oxaliplatin discontinuation in patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer: an ACCENT/IDEA pooled analysis of 11 trials.

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p &lt; 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p &lt; 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) &lt; 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p &lt; 0.001 and HR: 1.51 95%CI 1.31-1.74, p &lt; 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.

Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study

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. CLINICALTRIALS. NCT03422601; EudraCT Number: 2009-010384-16.

LBA30_PR - Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration

BackgroundctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months). MethodsctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned. ResultsOf the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA+(13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p=0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p<0.001). Adjuvant treatment for 6 months was superior to 3 months in both ctDNA– (HR :0.69 (95%CI 0.52 to 0.93) p=0.015) and ctDNA+ pts (HR: 0.50 (95%CI 0.27 to 0.95) p=0.033). Interestingly ctDNA+ pts treated 6 months had a similar prognosis to ctDNA- pts treated 3 months. ConclusionsIn this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Schøler LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] André T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219. Clinical trial identificationNCT00958737. Legal entity responsible for the studyGercor-Prodige. FundingClinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France). DisclosureJ. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

Oxaliplatin-based chemotherapy is associated with debilitating peripheral sensory neuropathy (PSN) for patients with stage III colon cancer. To assess disease-free survival (DFS) and long-lasting PSN in patients treated with 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. An open-label, multicenter, phase 3 randomized clinical trial of 1313 Asian patients with stage III colon cancer was conducted investigating the noninferiority of 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. From August 1, 2012, to June 30, 2014, participants were randomized to the 2 treatment groups. Data were analyzed from July 2017 to June 2018. Patients were randomized to receive 3 or 6 months of adjuvant chemotherapy. The choice of chemotherapy regimen, with the drugs modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine plus oxaliplatin (CAPOX), was at the discretion of the treating physician. The primary outcome was DFS. Secondary end points included the evaluation of PSN for up to 3 years and overall survival. Of the 1313 patients (651 were women and mean age was 66 [range, 28-85] years) enrolled and randomized, 22 were not treated because 10 were unable to begin treatment within 2 weeks of enrollment, 7 withdrew their consent, and 5 were not treated for various other reasons. Of 1291 patients treated (650 in the 3-month arm and 641 in the 6-month arm), 969 (75%) received the chemotherapy drug CAPOX. The hazard ratio (HR) for DFS of the 3-month arm compared with the 6-month arm was 0.95 (95% CI, 0.76-1.20). Hazard ratios were 1.07 (95% CI, 0.71-1.60) and 0.90 (95% CI, 0.68-1.20) for the drugs mFOLFOX6 and CAPOX, and 0.81 (95% CI, 0.53-1.24) and 1.07 (95% CI, 0.81-1.40) for patients with low-risk disease (TNM classification stages T1-3 and N1) and high-risk disease (stages T4 or N2), respectively. The rates of any grade of PSN lasting for 3 years in the 3-month vs 6-month treatment arms were 9.7% vs 24.3% (P < .001). Incidence of PSN lasting for 3 years was significantly lower for patients treated with CAPOX than for patients treated with mFOLFOX6 in both the 3-month (7.9% vs 15.7%; P = .04) and 6-month arms (21.0% vs 34.1%; P = .02). The incidence of long-lasting PSN was significantly lower for 3 months than for 6 months of therapy, and significantly lower for treatment with the drug CAPOX than with mFOLFOX6. Since the shortened therapy duration did not compromise outcomes, a 3-month course of CAPOX may be the most appropriate treatment option, particularly for patients with low-risk disease. UMIN Clinical Trials Registry: UMIN000008543.

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

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&lt;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&lt;0.001). In univariable analysis, IS was also associated with DFS in 6 months arm (p&lt;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.

Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration numberUMIN000008543, Results.

LBA24 - Efficacy of 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer (CC): Results from phase III ACHIEVE trial as part of the International Duration Evaluation of Adjuvant therapy (IDEA) Collaboration

LBA24 - Efficacy of 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer (CC): Results from phase III ACHIEVE trial as part of the International Duration Evaluation of Adjuvant therapy (IDEA) Collaboration

Phase III trial comparing 3–6 months of adjuvant FOLFOX4/XELOX in stage II–III colon cancer: safety and compliance in the TOSCA trial

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607.

Adjuvant Chemotherapy for Colon Cancer: Guidelines and Clinical Trials in Japan

In Japan, adjuvant chemotherapy for colon cancer was mainly developed using oral fluoropyrimidines. However, all Japanese studies to date have failed to demonstrate a statistically significant survival benefit of adjuvant chemotherapy with a combination of uracil and tegafur (UFT) monotherapy over surgery alone in patients with stage II or III colon cancer. The non-inferiority trials comparing different oral fluoropyrimidine monotherapies showed any fluoropyrimidine except S-1 was comparable in patients with stage III colon cancer. Japanese guideline plays an important role in the distribution of the optimal adjuvant treatment. In addition, the tolerability of oxaliplatin-based adjuvant chemotherapy was confirmed, and a multigene assay was validated in Japanese patients. A global collaboration is ongoing to test whether disease-free survival with 3 months of oxaliplatin-based adjuvant chemotherapy was non-inferior to that with 6 months of identical chemotherapy in patients with stage III or high-risk stage II colon cancer and is one of the best model task forces for the coordination of future adjuvant chemotherapy regimens in patients with colon cancer. These findings and further research will help define treatment duration and patient selection criteria for the personalization of adjuvant chemotherapy for colon cancer.

O-010 An international phase III randomized, non-inferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer: compliance and safety of the phase III Japanese ACHIEVE trial

O-010 An international phase III randomized, non-inferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer: compliance and safety of the phase III Japanese ACHIEVE trial

An international phase III randomized, non-inferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer: Compliance and safety of the phase III Japanese ACHIEVE trial.

3550Background: Oxaliplatin/Fluoropyrimidine chemotherapy is an established adjuvant treatment for colon cancer (CC). Neurotoxicity from oxaliplatin is cumulative, dose limiting, and potentially ir...

Toxicity and quality of life data from SCOT: An international phase III randomized (1:1) noninferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy.

Toxicity and quality of life data from SCOT : An international phase III randomized (1:1) noninferiority trial comparing 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy.

P0140 Second line aflibercept/folfiri chemotherapy in metastatic colorectal cancer in a single institution in a south east asian country: A case series

Background The safety and cost-effectiveness of aflibercept, approved in combination with fluorouracil/irinotecan chemotherapy (FOLFIRI) in treating patients with metastatic colorectal cancer (mCRC) after failure to oxaliplatin-based regimen, is largely unknown in our patient setting. We report the efficacy and safety of aflibercept/FOLFIRI, used in the second line setting in a series of mCRC patients at our institution. Methods This consecutive case series included all patients who fulfilled the aflibercept patient assistance programme (PAP) inclusion and exclusion criteria. We recorded data on demography, tumour, and prior treatment characteristics, aflibercept-related adverse events and treatment outcome. We measured 24-h urine protein, blood pressure, full blood count, liver and kidney function tests at baseline and at each aflibercept cycle. We assessed tumour response with serum CEA and CT scan after the forth to sixth treatment cycle. We reported severe adverse events (SAE) in the PAP SAE reporting documents. Findings From October 2012 to January 2014, out of nine patients granted approval by the PAP, five failed oxaliplatin-based regimen for mCRC while four progressed within 6 months of oxaliplatin-based adjuvant chemotherapy. Mean age was 54 (range 48–68). Two patients died before commencing therapy, leaving seven patients assessable for efficacy and safety analyses. Median number of cycles was five (range 1–11). At the sixth cycle, three patients had progressive disease and three had disease stabilisation. A decrease in CEA was observed in all three patients who achieved disease stabilisation. One patient has died, one patient remains on therapy while five patients remain alive, achieving survival duration of between 2–18 months at the time of analysis. Grade 3–4 adverse events were as follows: neutropenia, 5.26%; urinary tract infection, 5.26%; perinephric infection, 2.63%; proteinuria, 7.89%; scrotal ulcer, 2.63%; hypertension, 2.63%. No treatment-related deaths were observed. Interpretation Aflibercept seems to be a modestly effective regimen with acceptable toxicity in our small case series.