Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Resilience, Social Support, and Anxious Preoccupation in Patients with Advanced Cancer during COVID-19 Pandemic.

This study examines the mediating role of social support between anxious preoccupation and resilience in patients with cancer during COVID-19. NEOetic_SEOM is a prospective, multicenter study involving individuals with advanced, unresectable cancer who completed the following scales: Resilience (BCRS), Social Support (Duke-UNC-11), and anxious preoccupation subscale of the Mini-Mental Adjustment to Cancer (M-MAC) before starting antineoplastic treatment. Between March 2020 and July 2021, 507 patients (55% male; mean age, 65) were recruited. No differences in resilience were observed based on sociodemographic or clinical characteristics. Social support in people with advanced, unresectable cancer promotes both decreased anxious preoccupation and greater resilience.

Psychological distress and resilience in patients with advanced cancer during the Covid-19 pandemic: the mediating role of spirituality.

BACKGROUND: The purpose of this study was to investigate the sociodemographic factors related to psychological distress, spirituality, and resilience, and to examine the mediating role of spirituality with respect to psychological distress and resilience in patients with advanced, unresectable cancer during the Covid-19 pandemic. METHODS: A prospective, cross-sectional design was adopted. Data were collected from 636 participants with advanced cancer at 15 tertiary hospitals in Spain between February 2019 and December 2021. Participants completed self-report measures: Brief Resilient Coping Scale (BRCS), Brief Symptom Inventory (BSI-18), and Spiritual well-being (FACIT-Sp). Hierarchical linear regression models were used to explore the mediating role of spirituality. RESULTS: Spirituality was significantly different according to the person's age and marital status. Psychological distress accounted for 12% of the variance in resilience (ß = - 0.32, p < 0.001) and spirituality, another 15% (ß =0.48, p < 0.001). Spirituality acted as a partial mediator in the relationship between psychological distress and resilience in individuals with advanced cancer. CONCLUSIONS: Both psychological distress and spirituality played a role in resilience in cases of advanced cancer. Spirituality can help promote subjective well-being and increased resilience in these subjects.

Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain.

PURPOSE: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers. METHODS: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. RESULTS: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. CONCLUSION: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved. TRIAL REGISTRATION: Not applicable.

Toxicities and Quality of Life during Cancer Treatment in Advanced Solid Tumors.

The purpose of the study was to identify subgroups of advanced cancer patients who experienced grade 3-4 toxicities as reported by their oncologists as well as identify the demographic, clinical, and treatment symptom characteristics as well as QoL outcomes associated with distinct profiles of each patient. A prospective, multicenter, observational study was conducted with advanced cancer patients of 15 different hospitals across Spain. After three months of systemic cancer treatment, participants completed questionnaires that evaluated psychological distress (BSI-18), quality of life (EORTC QLQ-C30) and fatigue (FAS). The most common tumor sites for the 557 cancer patients with a mean age of 65 years were bronchopulmonary, digestive, and pancreas. Overall, 19% of patients experienced high-grade toxicities (grade 3-4) during treatment. Patients with recurrent advanced cancer, with non-adenocarcinoma cancer, undergoing chemotherapy, and a showing deteriorated baseline status (ECOG > 1) were more likely to experience higher toxicity. Patients who experienced grade 3-4 toxicities during cancer treatment had their treatment suspended in 59% of the cases. Additionally, 87% of the patients had a dose adjustment or a cycle delayed in their treatment due to a high risk of dying during treatment. Future research should focus on identifying interventions to reduce high-grade toxicities and improve quality of life in cancer patients.

The Role of Financial Difficulties as a Mediator between Physical Symptoms and Depression in Advanced Cancer Patients.

Financial difficulties experienced by cancer patients negatively impact the mental health of the patients. The objective of this study was to examine the mediating role of financial difficulties between physical symptoms and depression in patients with advanced cancer. A prospective, cross-sectional design was adopted in the study. The data were collected from 861 participants with advanced cancer in 15 different tertiary hospitals in Spain. The participants' socio-demographic characteristics were collected using a standardized self-report form. Hierarchical linear regression models were used to explore the mediating role of financial difficulties. In the results, 24% of patients reported a high level of financial difficulties. Physical symptoms were positively associated with financial difficulties and depression (ß = 0.46 and ß = 0.43, respectively), and financial difficulties was positively associated with depression (ß = 0.26). Additionally, financial difficulties played a role in explaining the relationship between physical symptoms and depression, showing a standardized regression coefficient of 0.43 which decreased to 0.39 after the financial difficulties were controlled. Healthcare professionals should consider the importance of providing financial resources and emotional support to help patients and their families cope with the financial burden associated with cancer treatment and its symptoms.

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy.

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13-8.25] and 14.0 months (95% CI, 13.0-14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578-0.636) and 0.623 (95% CI, 0.594-0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.

Uncertainty and hope in relation to anxiety and depression in advanced lung cancer.

OBJECTIVES: Intolerance of uncertainty (IU) has been linked to greater psychological distress, whereas hope appears to act as a protective factor against in patients with cancer. The aim of this study is to analyse the modifying effect of uncertainty in the presence of anxiety and depression in patients with advanced lung cancer. METHODS: Multicentre, prospective, observational, cross-sectional study of 145 individuals with advanced lung cancer. Participants completed the following questionnaires: IU Scale, Hert Hope Index, Brief Symptom Inventory. RESULTS: Among patients with advanced lung cancer, anxiety and depression were prevalent, 30% and 35%, respectively. Uncertainty and hope with respect to their illness negatively affected their psychological distress. Hope and uncertainty accounted for 22% of the variance in anxiety and 34% of depressive symptoms. The hypothesised modifying effects (uncertainty×hope) was not supported in the depressive and anxious symptom models. CONCLUSIONS: Our findings indicate that hope and uncertainty are important considerations in understanding mental health in people diagnosed with advanced lung cancer. Identifying patients who lack the resources needed to manage uncertainty and hope in relation to their disease could inform psychosocial intervention provision to improve quality of life.

Stoic attitude in patients with cancer from the NEOcoping study: Cross-sectional study.

AIM: Stoicism has been applied to describe a wide range of behaviors in the face of disease and influences an individual's use of coping strategies. This study tested the relationship between stoicism and social support, optimism, psychological distress, and coping strategies in patients with cancer. METHOD: NEOcoping is a multicenter, cross-sectional study. Participants' data were collected using a standardized, self-report form and LSS, MSPSS, Mini-MAC, BSI-18, and LOT-R questionnaires. Linear regression analyses were used to assess the association between stoicism and distress scores in both genders. A total of 932 individuals with non-metastatic, resected cancer were recruited. RESULTS: Males perceived a higher risk of recurrence and toxicity with adjuvant chemotherapy and obtained higher stoic attitude scores than females. Women scored higher on somatization, depression, and anxiety. Patients with high stoicism scores were older and experienced more maladaptive coping (helplessness, anxious preoccupation), and depression, while those with lower stoicism scores had greater perceived social support, optimism, and positive attitude. In both males and females, stoicism correlated negatively with perceived social support, optimism, and positive attitude, and positively with helplessness, anxious preoccupation, and depression. In men, stoicism was directly and negatively associated with social support and optimism, and positively with anxious preoccupation. In women, stoicism was positively associated. In women, stoicism was directly and negatively associated with social support and positively with age and optimism. Stoicism was directly and positively associated with helplessness. DISCUSSION: A stoic attitude was associated with lower social support, reduced optimism, and passive coping strategies (helplessness and anxious preoccupation) in this series of patients with cancer.

Fatigue, Emotional Distress, and Illness Uncertainty in Patients with Metastatic Cancer: Results from the Prospective NEOETIC_SEOM Study.

A cancer diagnosis can have a substantial impact on a patient's mental health and quality of life. The aim of this study was to investigate the prevalence of fatigue, emotional distress, and uncertainty and examine the predictive value they have on the quality of life of advanced cancer patients. A prospective, multicenter study was conducted between February 2020 and May 2021 of individuals diagnosed with an advanced, unresectable neoplasm prior to initiating systemic antineoplastic treatment. Participants completed questionnaires to quantify fatigue, emotional distress, disease uncertainty, and quality of life. A linear regression analysis was performed to study the predictive QoL variables. The study population comprised 508 patients, 53.7% of whom were male and had a mean age of 54.9 years. The most common cancers were digestive (40.6%), bronchopulmonary (29.1%), and breast (8.5%); the most frequent histology was adenocarcinoma (63%); and most were stage IV (79.7%). More than half (55.7%) suffered fatigue, and 47.7% exhibited emotional distress; both were more prevalent among women. Fatigue, emotional distress, and disease uncertainty all correlate with diminished quality of life. Similarly, ECOG performance status and the demographic variables of age, sex, and comorbidities impacted quality of life. This patient sample displayed a high prevalence of fatigue and emotional distress, together with illness uncertainty, which are clearly linked to waning quality of life. To decrease the experience of fatigue and improve mental health treatment in cancer patients, interventions based on a biopsychosocial model must be intensified.

Perceived Dignity of Advanced Cancer Patients and Its Relationship to Sociodemographic, Clinical, and Psychological Factors.

Objective: Loss of dignity is one of the main reasons for wishing for an early death in patients with incurable diseases such as cancer and is strongly associated with psychological distress and loss of quality of life. The present study aims to analyze the perceived dignity of patients with advanced cancer undergoing systemic treatment and their relationship with sociodemographic, clinical, and psychological factors. Methods: A prospective, cross-sectional, multicenter study was conducted in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and Palliative Patients' Dignity Scale, Brief Symptom Inventory, Mental Adjustment to Cancer, Functional Social Support Questionnaire, and Illness Uncertainty. Results: A total of 508 patients were recruited between February 2020 and October 2021. Most were male, aged > 65 years, with digestive tumors (41%), and metastatic disease at diagnosis. Subjects were classified as having low (56%, N = 283) or high (44%, N = 225) perceived dignity. Patients ≥ 65 years, with worse baseline status (ECOG ≥ 1), and worse estimated 18-month survival had lower levels of perceived dignity. People with lower perceived dignity scored higher for anxious preoccupation and hopelessness and lower for positive attitude. They also displayed higher levels of anxiety, depression, and somatic symptoms, greater uncertainty, and less social support. Conclusion: Self-perceived dignity in advancer cancer patients is significantly associated with psychological factors, psychological distress, uncertainty, less social support. Knowledge of these specific interactions is importance for adequate, comprehensive palliative care.

Role of sex on psychological distress, quality of life, and coping of patients with advanced colorectal and non-colorectal cancer.

BACKGROUND: Patients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications. AIM: To evaluate psychological distress, quality of life, and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex. METHODS: A prospective, transversal, multicenter study was conducted in 203 patients; 101 (50%) had a colorectal and 102 (50%) had digestive, non-colorectal advanced cancer. Participants completed questionnaires evaluating psychological distress (Brief Symptom Inventory-18), quality of life (EORTC QLQ-C30), and coping strategies (Mini-Mental Adjustment to Cancer) before starting systemic cancer treatment. RESULTS: The study included 42.4% women. Women exhibited more depressive symptoms, anxiety, functional limitations, and anxious preoccupation than men. Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men. Men with colorectal cancer reported the best health status. CONCLUSION: The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm. Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option.

Long term control stereotactic body radiotherapy (SBRT) for oligometastatic colorectal cancer: a single center study.

BACKGROUND: To evaluate survival after stereotactic body radiotherapy (SBRT) as radical treatment for metastases of colorectal cancer (CRC) and to identify prognostic factors after treatment. METHODS: Patients with metastatic CRC treated with SBRT on metastatic lesions were retrospectively analyzed between February 2012 and August 2016 at the General University Hospital of Valencia. The follow-up was carried out until July 15, 2018. The data have been collected in a database. Patients may have received prior systemic therapy and/or resection of metastatic disease. Endpoints were timed from end of SBRT and included overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: A total of 49 patients were identified. Before SBRT, 77.5% of the patients have received systemic therapy and 65.2% surgery for metastatic disease. Of metastatic lesions treated with SBRT 53.1% were located in the lung, 30.6% in the liver and 16.3% in other locations. Median survival were: PFS after treatment with SBRT was 9.9 months (95% CI: 4.64-15.1) and the median OS was 28.9 months (95% CI: 19.0-38.7). No relapses were observed in 20% of the patients after SBRT. The treatment was well tolerated and no patient had grade 3 or 4 adverse effects. Right colon [HR 16.53 (95% CI: 3.11-87.87), P value 0.001] and higher tumor stage (III-IV) [HR 12.30 (95% CI: 2.10-71.92), P value 0.005] showed a lower OS in a multivariate analysis. CONCLUSIONS: SBRT for oligometastatic disease is an effective option for patients with advanced CRC, with encorauging survival outcomes. However, a definitive validation in large randomized studies is required.

Diagnostic-therapeutic management of bile duct cancer.

Biliary tract cancer, or cholangiocarcinoma, comprises a heterogeneous group of malignant tumors that can emerge at any part of the biliary tree. This group is the second most common type of primary liver cancer. Diagnosis is usually based on symptoms, which may be heterogeneous, and nonspecific biomarkers in serum and biopsy specimens, as well as on imaging techniques. Endoscopy-based diagnosis is essential, since it enables biopsy specimens to be taken. In addition, it can help with locoregional staging of distal tumors. Endoscopic retrograde cholangiopancreatography is a key technique for the evaluation and treatment of malignant biliary tumors. Correct staging of cholangiocarcinoma is essential in order to be able to determine the degree of resectability and assess the results of treatment. The tumor is staged based on the TNM classification of the American Joint Committee on Cancer. The approach will depend on the classification of the tumor. Thus, some patients with early-stage disease could benefit from surgery; complete surgical resection is the cornerstone of cure. However, only a minority of patients are diagnosed in the early stages and are suitable candidates for resection. In the subset of patients diagnosed with locally advanced or metastatic disease, chemotherapy has been used to improve outcome and to delay tumor progression. The approach to biliary tract tumors should be multidisciplinary, involving experienced endoscopists, oncologists, radiologists, and surgeons.

Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy.

PURPOSE: RAS and BRAF mutations can be detected as a mechanism of acquired resistance in circulating tumor (ct) DNA in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor therapy. METHODS: RAS and BRAF mutational status was assessed in ctDNA in a baseline plasma sample and a serum sample collected at the time of the last available determination (named secondary extraction) from patients with KRAS exon 2 wild-type metastatic colorectal cancer treated in two first-line prospective biomarker-designed clinical trials (PULSE, ClinicalTrials.gov identifier: NCT01288339; and POSIBA, ClincialTrials.gov identifier: NCT01276379). RESULTS: Analysis of extended RAS and BRAF in tissue and plasma from 178 patients with KRAS exon 2 wild-type metastatic colorectal cancer showed a sensitivity of 64.1% and a specificity of 90%. The median overall survival (OS) of baseline patients with RAS and BRAF mutations in ctDNA was 22.3 months (95% CI, 15.6 to 29 months) and 8.9 months (95% CI, 6.3 to 11.4 months), respectively, which was significantly inferior to the median OS of 40.4 months (95% CI, 35.9 to 44.9 months) in two patients with wild-type disease (P < .001). Acquisition of RAS/BRAF mutations occurred in nine of 63 patients (14%) with progressive disease (PD; ie, blood draw within 1 month before PD or after PD) compared with six of 73 patients (8%) with no PD or blood extraction for ctDNA analysis before 1 month of PD (P = .47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (95% CI, 19.7 to 27.9 months) compared with 40.6 months (95% CI, not reached to not reached) in patients who remained free of mutations (P = .016). CONCLUSION: Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates survival. The emergence of RAS/BRAF mutations has limited relevance for the time to progression to anti-epidermal growth factor receptor therapy.

Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients.

INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP.

Role of RAS mutation status as a prognostic factor for patients with advanced colorectal cancer treated with first-line chemotherapy based on fluoropyrimidines and oxaliplatin, with or without bevavizumab: A retrospective analysis.

The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed. We investigated the association between the RAS mutation status and clinical outcomes in terms of response rate, progression-free survival (PFS) and overall survival (OS). Mutations in RAS genes were observed in 47 (52.6%) patients (45 KRAS and 2 NRAS mutations). Patients with tumours harbouring RAS mutations were less suitable for primary tumour resection, were more likely to develop lung metastases, and received bevacizumab treatment for a shorter time period compared with those with wild-type tumours. The response rate to chemotherapy did not differ according to the RAS mutation status, and there were no significant differences in PFS [RAS mutation: 12 months, 95% confidence interval (CI): 8.7-15.2 vs. RAS wild-type: 12 months, 95% CI: 9.67-14.32; P=0.857] or OS (RAS mutation: 20 months, 95% CI: 14.3-25.6 vs. RAS wild-type: 24 months, 95% CI: 18.7-29.2; P=0.631). Patients with RAS mutation vs. those with RAS wild-type exhibited a favourable trend in PFS when treated with bevacizumab (13 months, 95% CI: 6.5-19.4 vs. 10 months, 95% CI: 4.2-15.7, respectively; P=0.07) and OS (27 months, 95% CI: 18.5-35.4 vs. 15 months, 95% CI: 12.4-17.5, respectively; P=0.22). In conclusion, RAS mutations are not a prognostic marker for PFS and OS in CRC patients receiving fluoropyrimidine-oxaliplatine treatment, with or without bevacizumab. RAS mutations are not predictive of the lack of efficacy of bevacizumab, and these patients appear to benefit from anti-angiogenic treatment.

Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community

Introduction The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. Patients and methods This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. Result 122 patients with a median age of 61 years were included. 89% of patients had PS 0–1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74–6.15 months) and 10.15 (95% CI 7.47–12.82 months), respectively. Disease control rate 59.8%. The most common grade 3–4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58–17.32) in patients with hypertension vs 7.78 (95% CI 5.02–10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. Conclusions Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response (AU)