Survival In Metastatic Colorectal Cancer Research Articles

Influence of primary tumor location and resection on survival in metastatic colorectal cancer.

BACKGROUNDPatients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting.AIMTo explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL.METHODSWe retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.RESULTSFour hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.CONCLUSIONIn mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.

8P STC1, a baseline predictive biomarker for overall survival in metastatic colorectal cancer (mCRC)

8P STC1, a baseline predictive biomarker for overall survival in metastatic colorectal cancer (mCRC)

ASO Author Reflections: Mismatch Repair and Survival in Metastatic Colorectal Cancer.

ASO Author Reflections: Mismatch Repair and Survival in Metastatic Colorectal Cancer.

Prognostic role of visceral fat for overall survival in metastatic colorectal cancer: A pilot study

Body composition, has been established as a risk factor for colorectal cancer diagnosis and disease progression. Aim of this study was to investigate the prognostic role of adiposity, especially visceral fat (VAT), in patients (pts) with metastatic colorectal cancer (MCRC). A retrospective cohort of 71 MCRC pts treated between 2013 and 2017 was evaluated. VAT was measured as cross-sectional (cm2) area at the L3 level divided by the square of the height (m2). A ROC analysis was performed to define a prognostic threshold according to VAT. Before first-line therapy start, 40pts (56%) had a body mass index (BMI)>25kg/m2. The obtained cut-off value for VAT was 44. Median OS was 30.97 months. At univariate analysis, primary tumor resection (HR 0.40, p=0.029), VAT>44 (HR 2.85, p=0.011) and metastasectomy (HR 0.22, p=0.005) were significantly associated with OS. By multivariate analysis, VAT>44 (HR 2.6; p=0.020) and metastasectomy were still significantly associated with OS. This exploratory study suggests a prognostic role for VAT in MCRC pts, with higher VAT values predicting worse outcome.

Prognostic importance of primary tumor resection and synchronous metastasis on overall survival in metastatic colorectal cancer: Data from the FIRE-3 (AIO KRK-0306) study.

4070 Background: The FIRE-3 study (AIO KRK-0306) was designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. Overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Methods: In the present analysis of the FIRE-3 trial we explored the impact of primary tumor resection on outcome in relation to anti-EGFR vs. anti-VEGF treatment. Furthermore, we investigated the prognostic value of synchronous versus metachronous metastases. Results: In patients with synchronous disease no significant difference in OS was detected when comparing resected (n=339) vs. non-resected (n=97) patients (p-value: 0.29, HR: 1.17, 95%-CI: 0.88 – 1.55). In the cetuximab arm, resection (n=167) showed no significant benefit in OS when compared to non-resection (n=52) (p-value: 0.51, HR: 1.15, 95%-CI: 0.77 – 1.71). Treated with bevacizumab, similar results were present, when comparing resection (n=172) vs. non-resection (n=45); (p-value: 0.29, HR: 1.25, 95%-CI: 0.83 – 1.9). A strong trend was seen when comparing OS in treatment arms cet. (n=219) vs. bev. (n=217)) for patients with synchronous disease; (p-value: 0.05, HR: 1,26, 95%-CI: 1.0 - 1.59). 436/592 pts suffered from synchronous, 153/592 from metachronous disease (in 3/592 pts the information was not given). Median OS in pts with synchronous disease was 24.5 months and 29.5 in pts with metachronous disease (p-value: 0.02, HR: 0.76, 95%-CI: 0.6 - 0.96). In pts treated in the cetuximab arm metachronous disease (n=77) was associated with a trend towards longer OS when compared to synchronous disease (n= 219) (p-value: 0.13, HR: 0.76, 95%-CI: 0.54 – 1.1). The same effect was present in the bevacizumab arm (p-value: 0.05, HR: 0.73, 95%-CI 0.53 – 1.0) when comparing pts with synchronous disease (n=217) vs. pts. with metachronous disease (n=76). Conclusions: In the FIRE-3 study, metachronous disease was associated with superior OS compared to synchronous disease. This finding was accentuated in the bevacizumab arm. The role of resection of the primary tumor had no impact on survival. Clinical trial information: NCT00433927 .

20q amplification defined by genomic and clinical characteristics as a subgroup with increased prevalence and better survival in metastatic colorectal cancer.

e16003 Background: Genomic instability from 20q amplification is an oncogenic pathway in colorectal cancer (CRC). Several genes have been implicated, including BCL2L1, AURKA, SRC, ASXL1, GNAS and TOP1. There is a lack of data regarding 20q amplified group and one study implicating these genes suggested these patients have better overall survival. Next Generation Sequencing (NGS) has become widely used in metastatic CRC (mCRC) and easily identifies patients with 20q amplification. Nevertheless, most oncologists do not routinely consider 20q amplification status and this subgroup remains underinvestigated. This study aims to investigate genomic and clinical characteristics of 20q amplified mCRC using a single-center retrospective cohort and a multi-center genomic dataset. Methods: A cohort was identified comprising patients with mCRC who had NGS testing of tumor DNA and were treated between 2014-2019. Cases with and without 20q amplification were identified. Genomic, clinical and survival data were analyzed. Significant genomic findings were compared with all-stage CRC data using the AACR Genomic Evidence Neoplasia Information Exchange (GENIE) and The Cancer Genome Atlas (TCGA) databases. Results: Of the mCRC cohort ( n= 72), 15% ( n= 11) had 20q amplification. Amplified and non-amplified groups had no significant differences in age, sex or follow-up time. Patients with 20q amplification were more likely to have never smoked, and less likely to have treatment with targeted therapy. Survival analysis showed clear separation with longer overall survival for the amplified group. Eight genes at loci 20q11 to 20q13 were amplified - in order of frequency: ASXL1, GNAS, ARFRP1, ZNF217, AURKA, BCL2L1, SRC and TOP1. 20q amplification was significantly associated with wild-type RAS and BRAF, microsatellite stability, mutant TP53 and mutant APC. Using the GENIE and TCGA databases, it was found that metastatic disease had increased prevalence of all 20q amplified genes except TOP1, when compared to all-stage CRC. Conclusions: Clinical use of NGS identifies the 20q amplification subgroup that has increased prevalence in mCRC (compared to all CRC). Compared to non-20q amplified mCRC, this group had better survival, suggesting genomic pattern in mCRC is a novel independent prognostic marker. We believe mCRC patients would benefit from further studies defining a genomic prognostication model and development of therapy targeting the 20q amplification pathway.

Real-world evidence: Adjuvant chemotherapy in colorectal cancer with liver metastases.

e16008 Background: Systematic chemotherapy with biologics improves survival in metastatic colorectal cancer (mCRC). Oxaliplatin-based adjuvant chemotherapy is suggested in stage III and high-risk stage II CRC. However, whether adjuvant oxaliplatin-based chemotherapy remains standard treatment in CRC with liver metastases after hepatectomy is not elucidated. Methods: Medical records were searched in Chang-Gung Research Database from 2004 to 2017. Patients with CRC and liver metastases who received systematic therapies and salvage hepatectomy were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Total 454 patients received upfront hepatectomy (cohort 1) and 232 patients received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy (cohort 2) were included in this study. In cohort 1 or cohort 2, the baseline characteristics of those received either postoperative oxaliplatin-containing regimen or other systematic regimens were not statistically different in gender, age, primary site, and biologic drugs. In cohort 1, overall survival (OS) in those received postoperative oxaliplatin-containing chemotherapy was significantly better than that of those received non-oxaliplatin-containing chemotherapy (median OS: 6.6 vs. 4.5 years, Log-rank p = 0.032; 5-year survival rate: 57.5 vs. 47.0%). In cohort 2, OS in those received postoperative oxaliplatin-containing chemotherapy was similar with that of those received irinotecan or biologics-containing chemotherapy (median OS: 3.1 vs. 3.5 vs. 3.8 years, Log-rank p = 0.472; 5-year survival rate: 30.9 vs. 33.3 vs. 37.0%). Conclusions: Oxaliplatin-containing chemotherapy provides better OS and remains standard adjuvant treatment in CRC with liver metastases after upfront hepatectomy. However, adjuvant chemotherapy in those received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy should be individualized. Further prospective studies are warranted to validate these findings.

Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients

Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.

CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup.

Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated.Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated.Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS.Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.

Development and validation of an individualized gene expression-based signature to predict overall survival in metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a heterogeneous disease. Predictive biomarkers are in great demand to optimize patient selection at high risk for death and to provide a novel insight into potential targeted therapy. The present study retrospectively analyzed the gene expression profiles of tumor tissue samples from 4 public CRC cohorts, including 1 RNA-Seq data set from The Cancer Genome Atlas (TCGA) CRC cohort and 3 microarray data sets from GEO. Prognostic analysis was performed to test the predictive value of prognostic gene signature. Of 192 patients, 108 patients (56.3%) were men and median age was 65 years. A prognostic gene signature that consisted of 15 unique genes was generated in the discovery cohort. In the meta-validation cohorts, the signature significantly classified patients into high-risk and low-risk groups with regard to overall survival (OS) in mCRC patients with advanced stage disease and remained as an independent prognostic marker in multivariable analysis (1.57; 95% CI: 1.16-2.11; P=0.003) after adjusting for clinical parameters and molecular types. Gene Set Enrichment Analysis showed that several biological processes, including angiogenesis (P<0.001), epithelial mesenchymal transit (P<0.001) and inflammatory response (P=0.001), were enriched among this prognostic gene signature. The proposed prognostic gene signature is a promising prognostic tool to estimate OS in mCRC. Prospective larger studies to examine the clinical utility of the biomarkers to guide individualized treatment of mCRC are warranted.

Aggressive Multimodal Treatment and Metastatic Colorectal Cancer Survival

We aimed to assess patient and demographic factors, treatment trends, and survival outcomes of patients with colorectal cancer with metastasis to the liver, lung, or both sites. Differences remain among national guidelines about the optimal management strategy. Adults from the National Cancer Database (2010 to 2015) with a primary diagnosis of colorectal liver, lung, or liver and lung metastases were included and stratified by metastasis site. The primary end point was 5-year overall survival, analyzed using Kaplan-Meier survival curves, log-rank test, and the Cox proportional hazards model. Among 82,609 included patients, 70.42% had liver, 8.74% had lung, and 20.85% had simultaneous liver and lung metastases. Treatment with chemotherapy alone was used the most (21.11%), followed by chemotherapy with colorectal radical resection (CRRR) (19.4%), no treatment (14.35%), CRRR alone (9.03%), and chemotherapy with CRRR and liver/lung resection (8.22%). Patients with lung metastasis had significantly better 5-year overall survival rates than the other 2 metastatic groups (15.99%, 16.70%, and 5.51%; p < 0.001), even after stratifying by treatment type and adjusting for other factors. Chemotherapy with CRRR and liver/lung resection was associated with the greatest reduction in mortality risk for all sites in both unadjusted (35.15%, 44.52%, and 20.10%; p < 0.001) and adjusted analyses (hazard ratio 0.42; 95% CI, 0.38 to 0.47; p < 0.001; hazard ratio 0.31; 95% CI, 0.18 to 0.53; p < 0.001; and hazard ratio 0.79; 95% CI, 0.62 to 1.01; p= 0.064 for trend), and forgoing treatment or CRRR alone offered the worst overall survival. Patients with metastasis to lung had increased overall survival compared with other sites of metastases, regardless of treatment modality. Combined resection of primary tumor, metastasectomy, and chemotherapy appears to offer the greatest chance of survival.

PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer

ABSTRACT Background: Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. Methods: In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. Four patients are locally advanced and four are metastatic. All the patients received at least two doses of PD-1 antibody with or without chemotherapy as neoadjuvant therapy. The aim of the present study was to evaluate the short-term efficacy and toxicities of this strategy. Results: All the enrolled eight patients had a major response in imaging and/or pathological evaluation. Five of the seven resected patients were evaluated as pathological complete response. One patient without surgery has a clinical complete response (cCR) tumor response. Conclusions: Neoadjuvant PD-1 blockade induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H colorectal cancer. Further studies are required to evaluate the long-term effect of this strategy.

PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer.

84 Background: Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. Methods: In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. four patients are locally advanced and four are metastatic. All the patients received at least two doses of PD-1 antibody with or without chemotherapy as neoadjuvant therapy. The aim of the present study was to evaluate the short‐term efficacy and toxicities of this strategy. Results: Neoadjuvant PD-1 Blockade is well tolerated with a few immune-related side-effect profiles. All the enrolled patients had a major response in imaging and/or pathological evaluation. Five of the seven resected patients were evaluated as pathological complete response. One patient without surgery has a cCR tumor response. For the patients with radical surgery, there is no surgery-related complication observed. Conclusions: Neoadjuvant PD-1 blockade induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H colorectal cancer. Further studies are required to evaluate the long-term effect of this strategy.

621P - Biweekly TAS-102 and bevacizumab as a third-line chemotherapy for metastatic colorectal cancer: A phase II multicenter clinical trial (TAS-CC4 study)

BackgroundTAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab (BV) has been shown to extend median PFS to 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Furthermore, combination chemotherapy of TAS-102 plus BV was reportedly associated with grade ≥3 neutropenia in 72% of treated patients. This study was designed for patients being treated as 3rd line chemotherapy to investigate the clinical impact of this combination and whether neutropenia could be suppressed by altering the TAS-102 administration protocol (biweekly method). MethodsThis phase II study was conducted in investigator-initiated, open-label, single-arm, multicenter manner in Japan. Eligible patients were 20-80 years old and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; had previously administrated first- and second-line chemotherapy for mCRC and whose tumors were diagnosed as progression of disease (PD). TAS-102 (35mg/ m²) was given orally twice daily on days 1 -5 and 15 -19 in a 4-weeks cycle, and BV (5mg/ kg) was administered by intravenous infusion for 30min in every 2 weeks. The primary endpoint was PFS, and the secondary endpoints were response rate (RR), disease control rate (DCR), overall survival (OS), and safety. This study was registered at the University Hospital Medical Information Network, as UMIN#000030030. ResultsBetween January 1, 2018, and March 31, 2019, 45 patients with mCRC were enrolled in this study (median age, 63; male, 51%). The median PFS was 121 days. The RR and DCR were 4.4% and 73.3%, respectively. Grade 3 or higher adverse events were hypertension (20.0%), neutropenia (15.5 %), leukopenia (6.7 %), fatigue (6.7 %), anemia (4.4 %), anorexia (2.2 %), nausea (2.2 %), creatinine increased (2.2 %) and proteinuria (2.2 %). No treatment-related deaths occurred. ConclusionsBiweekly administration of TAS-102 and BV prevents neutropenia and could be one of the treatment options for 3rd line chemotherapy for mCRC. Clinical trial identificationUMIN000030030. 2018/March/01. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol

BackgroundCombination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients’ selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity.Methods/designCIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses’ duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients’ cetuximab-mediated ADCC and characterize the tumor microenvironment.DiscussionThe CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results’ interpretation as well as provide new insights in host-tumor interactions and cetuximab activity.Trial registrationThe CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number (NCT03874062).

Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study

IntroductionThe Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). ObjectiveThe objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. MethodsThis prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. ResultsA total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. ConclusionAlthough more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.

P-036 - Multidisciplinary approach associated with improved overall survival in metastatic colorectal cancer

P-036 - Multidisciplinary approach associated with improved overall survival in metastatic colorectal cancer

Retroperitoneal lymph node metastases as a prognosis factor in overall survival in metastatic colorectal cancer

Retroperitoneal lymph node metastases as a prognosis factor in overall survival in metastatic colorectal cancer

Impact of the addition of bevacizumab (Bev) to chemotherapy on survival in metastatic colorectal cancer (MCRC): A real-world population-based analysis.

e18215 Background: The addition of bev to IFL chemotherapy in MCRC was shown to improve survival in clinical trials, but its benefit in the real-world where it is frequently used with other systemic therapy regimens has not been fully evaluated. We aimed to assess the impact of bev on MCRC outcomes in a population-based setting. Methods: We examined all patients diagnosed with MCRC from a large Canadian province between 2004 and 2016. We categorized cases based on receipt of bev. Predictors of bev use were examined with multivariate logistic regression models. We also determined correlates of overall survival (OS) and disease specific survival (DSS) using Kaplan-Meier methods and Cox regression models, adjusting for measured confounders. Results: In total, 1,324 MCRC patients received systemic therapy. Median age was 68 years and 728 (55.0%) were men. Among them, 310 (23.4%) received bev. Younger age and better Charlson comorbidity score were associated with a higher likelihood of bev treatment (all p &lt; 0.05). In multivariate analysis, bevacizumab receipt did not correlate with OS or DSS for the entire cohort or for those who received bev with single agent chemotherapy (see Table). However, use of bev was correlated with improved outcomes for patients treated with oxaliplatin-based chemotherapy (HR for OS: 0.751 [0.571 – 0.987], p = 0.040; HR for DSS: 0.680 [0.502 – 0.920], p = 0.013), but worse outcomes for irinotecan-based chemotherapy (HR for OS: 1.327 [1.083 – 1.628], p = 0.006; HR for DSS: 1.309 [1.054 – 1.627], p = 0.015). Conclusions: Bev was only associated with improved survival when used with specific chemotherapy regimens. Table: Univariate and multivariate survival analysis for MCRC patients based on receipt of bevacizumab. m = median; (m) = months; HR = hazard ratio [Table: see text]

Metastasectomy and BRAF mutation: An analysis of survival outcome in metastatic colorectal cancer.

3531 Background: Surgical resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether such benefit is consistently observed for BRAF V600E mutant (MT) and wild type (WT) mCRC. We conducted a retrospective analysis to explore the influence of BRAF mutation status on survival outcomes after metastasectomy. Methods: Data collected from two large prospective population databases in Australia (Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and South Australian cancer registry). Overall survival (OS) and recurrence free survival (RFS) for BRAF MT and WT mCRC were evaluated by Kaplan-Meier method and compared by log-rank test. Results: 513 patients who had undergone metastasectomy were identified, 6% were BRAF MT. Median age 63. Metastasectomy rate was lower in BRAF MT (13 v 27%). In BRAF WT, 4% underwent resection of metastases (mets) in &gt;1 organ at diagnosis and 5% had 3 or 4 metastasectomies versus none in BRAF MT. Median OS in BRAF MT v WT: 25.7 v 48.5 months (HR 1.95; 1.18-3.22). In a multivariate model adjusting for variables which were significant on univariate analysis, OS differences were not statistically significant. Right primary tumor, intact primary, &gt;1 metastatic sites at diagnosis, non R0 resection, peritoneal mets and synchronous mets were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 v 19 months, p=0.09). Rate of downsizing was higher with triplet chemo than doublet +/- bevacizumab or doublet/EGFR in BRAF WT (50 v 30%) as well as MT (33 v 11%). Conclusions: Median OS was &gt; 2 years in BRAF MT V600E after metastasectomy in this study consistent with an OS benefit. OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Presence of BRAF MT should not impact patient selection for metastasectomy.[Table: see text]