Continuing education curriculums and outcomes on progressive metastatic colorectal cancer treatment.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 137-137
Author(s):  
Kinjal Parikh ◽  
Davecia Ragoonath Cameron ◽  
Pan Chen ◽  
Brittany Cain ◽  
Ann Carothers
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Progressive Disease ◽  
Statistical Significance ◽  
Treatment Options ◽  
P Value ◽  
Educational Activities ◽  
And Performance ◽  
To Receive

137 Background: The treatment armamentarium for patients with metastatic colorectal cancer (mCRC) has expanded significantly and treatment options for progressive disease remain limited. As data from clinical trials or subgroup analyses become available, landmark trials are published, and guideline recommendations or clinical utility of these therapies change, continuing medical education (CME) for oncologists is necessary to ensure that eligible patients continue to receive effective therapies. Methods: A series of 7 activities launched from 2016-2020 to reach a global oncology audience in the care of patients with mCRC. The educational activities included multi-modality approaches with didactics, cases, simulations, and panel discussions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls to measure changes in knowledge, competence, confidence, and performance. Oncologists who completed both the pre- and post-CME questions or who made relevant clinical decisions in the simulation activity were included in analysis and McNemar’s tests were conducted to assess statistical significance of the results with p < .05 being considered significant. The first activity launched on 6/8/2016 and the data reported were collected through 7/20/20. Results: As of 7/20/2020, 59,595 learners participated in the activities, including 18,634 total physician learners with 5,862 oncologists. Significant improvements in knowledge, competence, and confidence among oncologists, measured as relative % changes in correct responses or confidence from pre- to post-CME, were seen (n=60-214) [% pre, % post, p value]: 11%: knowledge regarding therapies for progressive disease in mCRC (83; 92; p < .05); 17%: knowledge of clinical trials assessing impact of patient/disease specific aspects on treatment selection (63; 74; p < .001); 11%: competence selecting therapy (55; 61; p < .05); 41%: confidence selecting therapy (34; 48; p < .001); 24%: confidence addressing communication barriers in mCRC (50; 62; p < .01). Significant improvement in performance of oncologists, measured as absolute % changes in pre- to post-CME correct responses were seen (n = 46) [% pre, % post, p value]: 28%: starting preferred treatment options (24; 52; p < .01); 18%: prescribing regorafenib (24; 43; p < .01); 9%: prescribing trifluridine + tipiracil (0; 9; p < .05). Conclusions: This series of online, expert-led, CME-certified educational activities resulted in significant improvement in knowledge, competence, confidence, and performance among learners regarding the management of patients with progressive metastatic colorectal cancer over time. These results demonstrate the effectiveness of on-demand education as new data emerge and indications expand to reinforce existing knowledge, close persistent gaps, and increase confidence in managing these patients.

An evaluation of RAS testing among metastatic colorectal cancer patients in the USA

2021 ◽  
Vol 17 (13) ◽  
pp. 1653-1663
Author(s):  
Laura Sangaré ◽  
Kimberly Delli-Zotti ◽  
Ana Florea ◽  
Marko Rehn ◽  
Al B Benson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Options ◽  
First Line ◽  
Background Data ◽  
The Usa ◽  
Testing Practices ◽  
Third Line ◽  
Colorectal Cancer Patients ◽  
To Receive

Background: Data on RAS testing practices prior to metastatic colorectal cancer (mCRC) treatment initiation are lacking in the USA. Materials & methods: Flatiron data were utilized for patients diagnosed with mCRC between 2011 and 2017. Flatiron is a longitudinal, demographically and geographically diverse database representing data from over 1.5 million active US patients treated at 255 community and hospital-affiliated oncology clinics. Results: Among 17,387 mCRC patients 69% were RAS tested and 31% were never tested. Timing of RAS testing was as follows: 23% were tested at the time of their initial CRC diagnosis, 60% following mCRC diagnosis but prior to first line of treatment, 3% prior to third line, the remaining 14% were tested following third line. Conclusion: A third (31%) of patients failed to receive RAS testing, therefore all treatment options were unavailable to them. These data highlight how universal testing has not been achieved.

Genes involved in EGFR-degradation to predict for efficacy in metastatic colorectal cancer patients treated with cetuximab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3557-3557
Author(s):  
Sebastian Stintzing ◽  
Wu Zhang ◽  
Takeru Wakatsuki ◽  
Yan Ning ◽  
Nico Benjamin Volz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Univariate Analysis ◽  
Resistance Mechanism ◽  
Progression Free Survival ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Free Survival ◽  
Receptor Endocytosis

3557 Background: As many transmembrane receptors, the epithelial growth factor receptor (EGFR) has a highly regulated turnover leading to inactivation and recycling or degradation after activation. This process can be divided into four different phases: receptor endocytosis, ubiquitation/neddylation, recycling and degradation. We tested whether functional significant single nucleotide polymorphisms in genes involved in the degradation pathway will predict clinical outcome (response, PFS and OS) in 108 patients with metastatic colorectal cancer enrolled in clinical trials and treated with cetuximab. Methods: Genomic DNA was isolated from blood from 108 patients treated with cetuximab enrolled in one of two clinical trials. All patients were KRAS and BRAF wildtyp. 20 SNPs were selected based on the involvement in receptor endocytosis (CBL, CIN85, endophilin) ubiquitation/neddylation, recycling and degradation (CBL, EPS15, Ubc12, UbcH7). Minor allele frequency had to by higher than 10%. PCR and product sequencing were done using standard procedures. Uni- and multivariate analyses, adjusting for age, gender, rash and racial background, were carried out. Results: In univariate analysis, rs895374 (HR: 1.69; p= 0.03), which is located in the exome of UbcH7, was able to separate patient cohorts significantly in perspective of progression free survival (CC = 5.7mo, CA= 3.6mo, AA= 3.4mo). Using multivariate analysis, rs895375 stayed to be a significant predictor of progression free survival with a Hazard ratio of 2.08 (95% CI 1.24 – 3.48) and a p value of 0.005. UbcH7 plays a pivotal role in the process of neddylation (adding NEDD8 to the EGFR), which switch the balance between recycling and degradation of the EGFR towards degradation. Conclusions: The process of EGFR recycling is important mechanism of resistance of cetuximab in colorectal cancer. This is the first report suggesting that germline polymorphisms in the degradation process may predict efficacy of cetuximab in patients with metastatic colorectal cancer. Anti-EGFR antibody like Sym004 might overcome this resistance mechanism by preventing EGFR recycling.

Application of the ASCO framework for assessing value in metastatic colorectal cancer clinical trials.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 687-687
Author(s):  
Doreen Anuli Ezeife ◽  
Sunil Parimi ◽  
Ellen R. Cusano ◽  
Matthew K Smith ◽  
Tony H. Truong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Pearson Correlation ◽  
Statistical Significance ◽  
Linear Regression Analysis ◽  
Health Benefit ◽  
Phase Iii ◽  
Multivariate Linear Regression Analysis ◽  
Nccn Guidelines

687 Background: Phase III trials (P3T) in metastatic colorectal cancer (mCRC) have collectively led to incredible advancements in patient outcomes over the past thirty years. It is unknown how many of these trials have led to clinically relevant improvements based on clinical benefit, toxicity and cost. Our objective was to characterize the evolution of mCRC P3T with the ASCO Value Framework. Methods: P3T of systemic therapy for mCRC published between 1980 and 2015 were identified. Data regarding the trial sample size, journal year of publication, statistical significance, journal impact factor, and citation by the 2015 mCRC National Comprehensive Cancer Network (NCCN) guidelines were extracted. For each trial, the Net Health Benefit (NHB) score was calculated using the June 2015 (original) and May 2016 (revised) ASCO Value Advanced Disease Frameworks. Data were analyzed to identify associations using the Chi-square, Kruskal-Wallis, and t-tests. Results: There were 108 mCRC P3T eligible for calculation of the original and revised NHB score. Median NHB score was 4.1, range -30 to 43.5, using the revised framework. Only 13% of trials received at least 10 bonus points for palliation, quality of life, or tail of the curve. The revised framework demonstrated moderate correlation with the original framework (Pearson correlation coefficient = 0.63, p<0.0001). NHB scores were normally distributed with the revised framework, unlike the original framework. Trials with significant results had significantly higher revised NHB scores (median NHB score 23.1 vs 2.5, p < 0.0001). Clinical trials cited in NCCN had higher revised NHB scores than those not cited (median NHB score 7.6 vs 0, p = 0.03). In multivariate linear regression analysis, the only significant predictor of a high revised NHB score was a statistically significant improvement in the primary outcome. Conclusions: Median revised NHB score for mCRC P3T was 4.1. Higher NHB scores were associated with significant studies and citation by NCCN guidelines, a surrogate for practice-changing trials. The revised ASCO Value Framework can be a useful tool to assess the value of new mCRC treatments.

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

scholarly journals A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2762
Author(s):  
Samantha Di Donato ◽  
Alessia Vignoli ◽  
Chiara Biagioni ◽  
Luca Malorni ◽  
Elena Mori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Stratification ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Early Stage ◽  
Prospective Trial ◽  
Proton Nuclear Magnetic Resonance ◽  
P Value ◽  
Resonance Spectroscopy ◽  
Metabolomic Fingerprinting

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

scholarly journals Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeong Hak Bang ◽  
Jeong Eun Kim ◽  
Ji Sung Lee ◽  
Sun Young Kim ◽  
Kyu-Pyo Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Medical Need ◽  
Significant Disease

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.

scholarly journals The Evolutionary Landscape of Treatment for BRAFV600E Mutant Metastatic Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 137
Author(s):  
Gianluca Mauri ◽  
Erica Bonazzina ◽  
Alessio Amatu ◽  
Federica Tosi ◽  
Katia Bencardino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Braf Inhibitor ◽  
Current Treatment ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Poor Prognostic Factor

The BRAFV600E mutation is found in 8–10% of metastatic colorectal cancer (mCRC) patients and it is recognized as a poor prognostic factor with a median overall survival inferior to 20 months. At present, besides immune checkpoint inhibitors (CPIs) for those tumors with concomitant MSI-H status, recommended treatment options include cytotoxic chemotherapy + anti-VEGF in the first line setting, and a combination of EGFR and a BRAF inhibitor (cetuximab plus encorafenib) in second line. However, even with the latter targeted approach, acquired resistance limits the possibility of more than an incremental benefit and survival is still dismal. In this review, we discuss current treatment options for this subset of patients and perform a systematic review of ongoing clinical trials. Overall, we identified six emerging strategies: targeting MAPK pathway (monotherapy or combinations), targeting MAPK pathway combined with cytotoxic agents, intensive cytotoxic regimen combinations, targeted agents combined with CPIs, oxidative stress induction, and cytotoxic agents combined with antiangiogenic drugs and CPIs. In the future, the integration of new therapeutic strategies targeting key players in the BRAFV600E oncogenic pathways with current treatment approach based on cytotoxic chemotherapy and surgery is likely to redefine the treatment landscape of these CRC patients.

scholarly journals Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neel I. Nissen ◽  
Stephanie Kehlet ◽  
Mogens K. Boisen ◽  
Maria Liljefors ◽  
Christina Jensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Collagen Type ◽  
Performance Status ◽  
Drug Uptake ◽  
Collagen Type Iii ◽  
Serum Samples ◽  
Type Iii ◽  
Poor Treatment ◽  
And Performance

AbstractA desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Radioembolization for Rare Metastatic Disease

2021 ◽  
Author(s):  
Andrew S. Niekamp ◽  
Govindarajan Narayanan ◽  
Brian J. Schiro ◽  
Constantino Pena ◽  
Alex Powell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Metastatic Colorectal Cancer ◽  
Treatment Modality ◽  
Treatment Options ◽  
Efficacy And Safety ◽  
Multiple Tumor ◽  
Tumor Types ◽  
Hepatic Malignancies ◽  
Yttrium 90

AbstractRadioembolization has become a widespread treatment modality for both primary and metastatic hepatic malignancies. Although the majority of data and indication for yttrium-90 radioembolization have been for hepatocellular carcinoma and metastatic colorectal cancer, radioembolization with yttrium-90 has rapidly expanded into the treatment options for multiple tumor types with metastases to the liver. This article reviews the clinical data and expanding utilization of radioembolization for rare metastatic diseases with an emphasis on efficacy and safety.

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