1) The document discusses treatment guidelines and clinical trials for metastatic colorectal cancer. It summarizes several studies evaluating different chemotherapy regimens and targeted therapies as first-line and second-line treatment options.
2) Location of the primary tumor is noted as an important factor in prognosis. Studies presented at ASCO 2016 evaluated the relationship between tumor location and outcomes with various treatments.
3) Ongoing research is exploring continuing anti-angiogenic therapies beyond progression and evaluating new combination regimens incorporating agents like ziv-aflibercept.
Biomarkers have a diversified role in diagnosis, prognostication and risk stratification. This presentation aims to compile the basic information and new literature on various biomarkers pertaining to cancer care.
Fight Colorectal Cancer’s Medical Advisory Board Member, Axel Grothey, MD, focused this webinar to stage III colon cancer patients. Dr. Grothey, medical oncologist at Mayo Clinic, will spend the hour discussing current treatment options and exciting new research that pertains to stage III colon cancer patients.
Speaker: Lisette Stork-Sloots, Sr Program Director at Agendia, discusses how their technology, MammaPrint was commercialized.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
What is biomarker?
What is the purpose of biomarker
Processes of biomarker development?
Types of Biomarkers
What is biomarker testing for cancer treatment?
Uses of Biomarkers in Cancer Medicine
Uses of Biomarkers in Cancer Drug Discovery
Biomarkers have a diversified role in diagnosis, prognostication and risk stratification. This presentation aims to compile the basic information and new literature on various biomarkers pertaining to cancer care.
Fight Colorectal Cancer’s Medical Advisory Board Member, Axel Grothey, MD, focused this webinar to stage III colon cancer patients. Dr. Grothey, medical oncologist at Mayo Clinic, will spend the hour discussing current treatment options and exciting new research that pertains to stage III colon cancer patients.
Speaker: Lisette Stork-Sloots, Sr Program Director at Agendia, discusses how their technology, MammaPrint was commercialized.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
What is biomarker?
What is the purpose of biomarker
Processes of biomarker development?
Types of Biomarkers
What is biomarker testing for cancer treatment?
Uses of Biomarkers in Cancer Medicine
Uses of Biomarkers in Cancer Drug Discovery
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Small Presentation where the benefit of addition of induction / neoadjuvant chemotherapy to concurrent chemoradiation in head neck cancers is explored.
In this presentation, I discuss a new standard of treatment in cancers which is immunotherapy. I also discuss the few cancers for which it has been approved.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Induction chemotherapy followed by concurrent ct rt versus ct-rt in advanced ...Santam Chakraborty
Small Presentation where the benefit of addition of induction / neoadjuvant chemotherapy to concurrent chemoradiation in head neck cancers is explored.
In this presentation, I discuss a new standard of treatment in cancers which is immunotherapy. I also discuss the few cancers for which it has been approved.
Green Building Academy is the academic division of M/s Conserve Green Building & MEP Solutions, Doha, Qatar established to cater the academic needs of construction sector, especially in Green Buildings, MEP, Energy Efficiency etc.
Můžete prožít šťastný život? Epideimie - také kolem vás všichni prskají akýchají? bydlení: Nevytvářejte sterilitu v interiéru, TAO - fáze sběru a ochrany - část II, Energie dní na týden od 31.10. 2016
La préfecture interdit toute manifestation aux abords du bar identitaire, samediJean-michel Neugate
Une manifestation contre l’ouverture de La Citadelle, le controversé bar identitaire situé rue des Arts, est prévue samedi à Lille. Mais le préfet Michel Lalande a décidé, ce jeudi, d’interdire les rassemblements près de cet établissement. Les riverains s’inquiètent.
Tratamiento inicial de pacientes posmenopáusicas con cáncer de mama HR+/her2-...Mauricio Lema
Versión 2 (definitiva): Presentado en la Clínica VIDA en 11.11.2016, por invitación de Jairo Estrada. Versión corregida (se corrigen errores en 3 diapositivas de la versión anterior).
Tratamiento inicial de cáncer de mama HR+/Her2- metastásico en postmenopáusicasMauricio Lema
Versión inicial (con errores): Presentado en junta de la Clínica VIDA, 11.11.2016. Invitado por Jairo Estrada. La versión corregida está en: http://www.slideshare.net/MauricioLema/tratamiento-inicial-de-pacientes-posmenopusicas-con-cncer-de-mama-hrher2-metastsico-una-visin-panormica
Squeezing Dr. Coleman: the answers with key evidenceMauricio Lema
Q&A session with Dr. Rob Coleman on practical issues, and treatmente patterns in ovarian cancer.
4th International Congress - Clinical de Oncología Astorga, Panamá, 27-29 de Junio, 2019
Molecular testing and tumor testing. Have you ever been asked about it? Have you wondered the importance of it, as it relates to your particular cancer? Have you ever wondered if you should or shouldn't have your tumor tested, and what that involves? Dr. Bekaii-Saab, MD will discuss the importance of testing the molecular biology of an individual patients tumor. How they do that and why it may or may not be important to have done. He will talk about how this is playing an even bigger role in choice of treatment options for patients now more than ever. And about the way physicians are making treatment choices based on each individuals molecular biology of their tumor.
Dr. Bekaii-Saab is the Section Chief, Gastrointestinal Oncology, James Cancer Hospital and Solove Research Institute. Dr. Bekaii-Saab is one of America’s Best Doctors. Additionally, he has been listed in U.S. News and World Report’s Top Doctors for multiple consecutive years. His research interests include experimental therapeutics/translational research focused on molecularly-targeted and immune-mediated therapies in gastrointestinal (GI) cancers. He is the principal investigator on numerous clinical trials, including studies supported through research grants from the National Cancer Institute (NCI) and the National Comprehensive Cancer Network (NCCN). Dr. Bekaii-Saab is the recipient of the prestigious NCI clinical investigator team leadership award and the ASCO leadership program development award.
Actualización en el abordaje terapéutico ante un cáncer colorrectal metastásicoMauricio Lema
Ponencia en el VII Congreso internacional de coloproctología, Bogotá, 18.08.2016. Con énfasis en los estudios recientes en terapia antiangiogénica, y el impacto del lado del primario en el pronóstico (y aspectos predictivos) de la enfermedad metastásica.
The Molecular Analysis on Circulating Tumor Cells to Determine Prognostic and...QIAGEN
Circulating tumor cells (CTCs) is an emerging source used molecular cancer diagnostics. Through expression profiling of CTCs, it allows a deeper understanding about which metabolic pathways enable tumor cells to survive in the circulation, how they become resistant to a drug regimen, how they transform and adapt and, finally, which cellular markers should targeted for future therapies.
This webinar will introduce the AdnaTest CTC detection platform which has been proven in several clinical trials to provide prognostic and predictive information in breast, ovarian and prostate cancer. The platform by itself is still open for research and allows access to any potential target of interest. Join us to learn more about this novel platform, its technology and applications in liquid biopsy.
Identification of cancer drivers across tumor typesNuria Lopez-Bigas
Thousands of tumor genomes/exomes are being sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and other initiatives. This opens the possibility to have, for the first time, a comprehensive picture of mutations, genes and pathways involved in the cancer phenotype across tumor types. We have developed computational methods able to identify signals of positive selection in the pattern of tumor somatic mutations, which point to genes and pathways directly involved in the development of the tumors. We have applied these approaches to 3025 tumors from 12 different cancer types of the TCGA Pan-Cancer project, identifying 291 high-confidence cancer driver genes acting on those tumors (Tamborero et al 2013). We have also developed IntOGen-mutations (http://www.intogen.org/mutations), a novel web platform for cancer genomes interpretations, which analyses not only TCGA pan-cancer data but all mutation data from ICGC and other initiatives. The resource allows users to identify driver mutations, genes and pathways acting on more than 6000 tumors originated in 17 different cancer sites and to analyze newly sequence tumor genomes. Among the novel cancer drivers identified there are chromatin regulatory factors and splicing factors, which are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment. In my talk I will summarize all these recent findings.
More info: http://bg.upf.edu/blog/2013/10/my-slides-on-identification-of-cancer-drivers-across-tumor-types/
Similar to Tratamiento de cáncer de colon metastásico: de las guías de práctica, genómica a la realidad (20)
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tratamiento de cáncer de colon metastásico: de las guías de práctica, genómica a la realidad
1. Tratamiento del cáncer colorectal metastásico: de las guías
de práctica clínica, pasando por la genómica y la realidad
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia
Cartagena, Colombia
09.07.2014
10. “Thou shall not use anti EGFR-agents
in mutated RAS CRC patients”
11. mCRC: ESMO Clinical Practice
Guidelines
http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Metastatic-Colorectal-Cancer
Group 0Group 0
Group 1Group 1
Group 2Group 2
Group 3Group 3
Resectable R0
Convertible
Unlikely
resectable/High
tumor burden
Never resectable
Surgery/ +/- Adj CTSurgery/ +/- Adj CT
Conversion CT/SurgeryConversion CT/Surgery
Conversion CT/SurgeryConversion CT/Surgery
Less-toxic CTLess-toxic CT
Cure
Cure
Long OS
QoL
Criticism: solely based on DISEASE characteristics
12. mCRC: ESMO Clinical Practice
Guidelines
http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Metastatic-Colorectal-Cancer
Group 0Group 0
Group 1Group 1
Group 2Group 2
Group 3Group 3
Resectable R0
Convertible
Unlikely
resectable/High
tumor burden
Never resectable
Surgery/ +/- Adj CTSurgery/ +/- Adj CT
Conversion CT/SurgeryConversion CT/Surgery
Conversion CT/SurgeryConversion CT/Surgery
Less-toxic CTLess-toxic CT
FOLFOX
FOLFOXIRI-Bev
FOLFIRI-Cet
FOLFOX-Bev
XELOX-Bev
FOLFOX-Cet
FOLFIRI-Cet
FP-Bev
Criticism: solely based on DISEASE characteristics
14. CAPOX +
Bevacizumab
6 meses
“Continuum of care” in mCRC – “blurring line descriptions”
Cape + Bevacizumab
Hasta progresión
1o
línea
FOLFIRI +
Bevacizumab
Oxaliplatino hasta neuropatía
QT + Bevacizumab
Hasta progresión
2o
línea
Cetuximab +/-
Irinotecán
Regorafenib
Hasta progresión
≥3o
línea (KRAS nativo)
Hasta progresión
CAIRO-3
TML
Cunningham D, et al. N Engl J Med 2004;351:337-45. CORRECT Trial (Van Cutsem 2012)
16. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
Mutations in KRAS, NRAS, and BRAF
Distribution and Prognostic Significance
BRAF mutation All patients
Any mutation
KRAS mutation
KRAS WT
All WT
Mutation Status
0
6
12
MedianPFS
(Mos)
Arm A Arm B
0
6
12
18
MedianOS
(Mos)
57
340
268
815
367
289
45
366
297
815
362
292
0
10
20
30
40
2-YrOS(%)
Prognostic Effect of Mutational Status
“All WT”
n = 581
(44%)
KRAS MT
n = 565
(43%)
NRAS MT
n = 50 (4%)
BRAF MT
n = 102 (8%)
Total
N = 1316 (81%)
554
11
39
10
2
Population n (%) Arm A Arm B
ITT 1630 815 815
Assessed for mutations 1316 648 668
KRAS mutation
NRAS mutation
BRAF mutation
565 (43)
50 (4)
102 (8)
268
18
57
297
32
45
KRAS WT 729 (55) 367 362
KRAS/NRAS/BRAF WT
“All WT”
581 (44) 289 292
Maughan TS, et al. ASCO 2010. Abstract 3502.
17. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
Phase III 80405 Trial: First-line CT + Either
Cetux or Bev in KRAS-WT mCRC
Primary endpoint: OS
Secondary endpoints: ORR, PFS, TTF, duration of response
Patients with mCRC
and KRAS WT
(codons 12, 13),
ECOG PS 0/1
(N = 1137)
FOLFOX or FOLFIRI +
Bevacizumab q2w
(n = 559)
ClinicalTrials.gov. NCT00265850. Venook AP, et al. ASCO 2014. LBA3..
FOLFOX or FOLFIRI +
Cetuximab q1w
(N = 578)
A third arm with CT + bevacizumab + cetuximab
was closed to accrual in September 2009
18. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
CALGB/SWOG 80405: OS in the ITT
Population
mOS (95% CI), mos
CT + Cetux 29.9 (27.0-32.9)
CT + Bev 29.0 (25.7-31.2)
HR 0.925 (0.78-1.09)
P = 0.34
Venook AP, et al. ASCO 2014. Abstract LBA3.
0
12 24 36 48 60 72
Mos
80
100
60
40
0
OS(%)
20
84
19. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
20. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
21. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
22. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
23. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
24. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.
25. The relationship between primary tumor sidedness and
prognosis in colorectal cancer. Deborah Schrag
Proc ASCO, 2016, 3505
.
26. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee
Proc ASCO, 2016, 3505
.
27. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee
Proc ASCO, 2016, 3505
.
28. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee
Proc ASCO, 2016, 3505
.
29. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee
Proc ASCO, 2016, 3505
.
30. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
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Phase III RAISE Study: Second-Line
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Patients with CRC
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Treat until PD or
unacceptable
toxicity
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(n = 536)
Placebo +
FOLFIRI q2w per cycle
(n = 536)
Stratified by geographic region, KRAS mutation
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Ramucirumab: anti-VEGFR2 antibody
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Editor's Notes
ITT, intention to treat; MT, mutation; OS, overall survival; PFS, progression-free survival; WT, wild-type
5-FU, 5-fluorouracil; BEV, bevacizumab; CT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; mCRC, metastatic colorectal cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival.
Let’s take a look at the data that’s really come forward for helping us manage patients with metastatic colorectal cancer. And in particular we’re going to focus on second line and beyond because there are a lot of new choices, a lot of new trials, new medicines that have come forward in this setting, and we want to give everybody a context of how to manage it. And really, there are a lot of choices for these patients. So let’s make sure we have good clarity on this.
Now the first of these studies that really came forward into the second line with biologics is known as the TML study, and the idea behind this was that if you were on bevacizumab in first line, could you continue it on through the second line and still demonstrate benefit?
CT, chemotherapy; BEV, bevacizumab; ECOG, Eastern Cooperative Oncology Group; ITT, intent to treat; OS, overall survival; PFS, progression-free survival; PS, performance score; TML, treatment with multiple lines.
And in a randomized clinical trial where half got the bevacizumab on through to second line, the other half did not, we showed a survival advantage for those patients—not a very big one, a 1.4‑month improvement in survival, but it’s been an important positive impact for patients through lines of therapy. So this really established anti‑VEGF therapy through lines of therapy, using bevacizumab. It also showed a progression‑free survival advantage in those patients.
ECOG, Eastern Cooperative Oncology Group; FOLFIRI, fluorouracil/leucovorin/irinotecan; mCRC, metastatic colorectal cancer; ORR, overall response rate; OS, overall survival; q2w, once every 2 weeks; PFS, progression-free survival; PS, performance status.
In a very similar design, the VELOUR study randomized patients in second line to FOLFIRI plus or minus ziv‑aflibercept. Very similar design to the TML. Some patients had had prior bevacizumab in this clinical trial, but it was not a requirement of this clinical trial.
FOLFIRI, fluorouracil/leucovorin/irinotecan; mCRC, metastatic colorectal cancer; OS, overall survival; PFS, progression-free survival.
And just like the TML study, a 1.4‑month improvement in overall survival and improvement in progression‑free survival.
AFL, aflibercept; FOLFIRI, fluorouracil/leucovorin/irinotecan; mCRC, metastatic colorectal cancer; OS, overall survival
When we look at the subset of patients who had had prior bevacizumab, we also see an improvement in outcome there, in both PFS and OS. So even if you’d had a VEGF inhibitor in the first line, this switching to a second VEGF inhibitor was still a positive impact and, of course, supported its approval in the United States and around the world for second-line treatment in combination with FOLFIRI.
CRC, colorectal cancer; FOLFIRI, fluorouracil/leucovorin/irinotecan; OS, overall survival; PD, progressive disease; TTP, time to progression.
Enrollment of at least 1050 patients with 756 events for 85% power; Hazard ratio of 0.8; Median overall survival of 10 months in the control arm vs 12.5 months with ramucirumab with a 2-sided α level of 0.05. And then comes along the third of these clinical trials and the third of these medicines, a medicine called ramucirumab. Also a monoclonal antibody, but it binds again to the receptor and not to the ligand, so slightly different mechanism of action, but exactly the same design again. Second‑line metastatic colon, FOLFIRI plus or minus ramucirumab in these patients.
FOLFIRI, fluorouracil/leucovorin/irinotecan; OS, overall survival; Ram, ramucirumab.
Yet again we see a one and a half or so month improvement in overall survival in those patients, and again the majority of these folks had had prior VEGF therapy as well.
Now I want to kind of end our discussion about the third line and beyond treatments, and a drug that we’ve had for a while now: regorafenib. You know this medicine. It’s a multitargeted tyrosine kinase inhibitor, hits a lot of different targets within cancer cells. We’re not really sure of the true mechanism of action for this drug.
BSC, best supportive care; mCRC, metastatic colorectal cancer; po, orally; qd, daily.
It has some VEGF activity and others, but it was tried in a randomized clinical trial known as the CORRECT study, 2:1 randomization against placebo, done around the world. And of course, this really sets a new stage for us, for the treatment of metastatic colon; this trial accrued very quickly. It showed us that there are a lot of these patients out there who’ve tried all their standard medicines and are now looking for new treatment options.
IQR, interquartile range; OS, overall survival; PFS, progression-free survival.
And it accrued, as I said, quickly, and it demonstrated an improvement in overall survival. Again, 1.4 months’ improvement and was enough to justify its approval both here in the United States and around the world. So it is a drug that has value, it controls our cancer in patients, and we should utilize it more.