Dr. Gail Eckhardt
Professor and Head of the Division of Medical Oncology at the University of Colorado Denver and Health Sciences Center.
Join us for an exciting webinar about pathways and targets. Dr. Eckhardt will discuss the basic of pathways within a cancer cell, and how (and why) they can affect treatment options for patients. She'll explain how we learn about how new pathways are discovered, and how this information tell us what drugs may work in certain patients and why some drugs don’t.
Dr. Eckhardt will discuss the idea of targeted therapies, and the difference between them and regular chemotherapy. She'll talk about the relationship between pathways and targeted drugs, and how this may impact drug development in the future.
Two new drugs for colorectal cancer may offer new hope for late stage patients, and they might hit the market in 2013.
Dr. Rich Goldberg, physician-in-chief of the Ohio State University Medical Center and a leader in colorectal cancer research is going to give you the straight facts about these drugs:
* What hope might they offer?
* What side effects do they cause?
* Will either be the right drug for you?
About Dr. Goldberg:
Dr. Richard Goldberg is an internationally renowned gastrointestinal oncologist and the physician-in-chief at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Institute (OSUCCC-James). He is a member and former chair of the National Cancer Institute Colorectal Task Force and an international leader in evaluating new agents for the treatment of colorectal cancer and researching inherited colorectal cancer syndromes
Join Dr. Emily Chan presentation on the latest research and treatments for colorectal cancer patients presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Two new drugs for colorectal cancer may offer new hope for late stage patients, and they might hit the market in 2013.
Dr. Rich Goldberg, physician-in-chief of the Ohio State University Medical Center and a leader in colorectal cancer research is going to give you the straight facts about these drugs:
* What hope might they offer?
* What side effects do they cause?
* Will either be the right drug for you?
About Dr. Goldberg:
Dr. Richard Goldberg is an internationally renowned gastrointestinal oncologist and the physician-in-chief at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Institute (OSUCCC-James). He is a member and former chair of the National Cancer Institute Colorectal Task Force and an international leader in evaluating new agents for the treatment of colorectal cancer and researching inherited colorectal cancer syndromes
Join Dr. Emily Chan presentation on the latest research and treatments for colorectal cancer patients presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Webinar: Transforming Operational Throughput – The Journey Toward Value-Based...Huron Consulting Group
At the 2014 Children’s Hospital Association Annual Leadership Conference, Huron Healthcare and Texas Children’s Hospital (TCH) presented an educational session on the journey toward value-based care.
In the presentation, Huron Healthcare managing director, Larry Burnett, TCH Senior Vice President, Tabitha Rice, and TCH Assistant Vice President of nursing, Jackie Ward, shared valuable insights from their work together at TCH. Focusing on insights and results from TCH’s engagement with Huron Healthcare, the presentation includes:
• Opportunities and results at TCH in areas including care management, care progression, patient placement, and care variation.
• Keys to driving results, successful change, and integrated care delivery
• Steps for a sustainable approach
Lung cancer, which accounted for 1.8 million cases in 2012, is a serious issue in Asia. While it is primarily driven by smoking, non-smoking lung cancer is also growing due to pollution and oncogenic mutation.
Find out more about the severity of lung cancer in China, Taiwan, India, and Korea in our latest Social Innovation Playbook Series on SlideShare
Is the future of medicine chemo pills? In this webinar, we will delve into oral chemotherapy and explain why some patients are offered the option to receive cancer treatment in a pill form. We’ll discuss the advantages and challenges of this emerging treatment option and highlight the current therapies some patients receive. Join us to learn more about the future of treating colorectal cancer via pills.
David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
El futuro del tratamiento del cáncer renal metastásico: inmunoterapia y terap...Mauricio Lema
Ponencia en el primer simposio de la Asociación Colombiana de Hematología y Oncología (ACHO) de cáncer genitourinario, Bogotá, septiembre 23 y 24 de 2016.
Webinar: Transforming Operational Throughput – The Journey Toward Value-Based...Huron Consulting Group
At the 2014 Children’s Hospital Association Annual Leadership Conference, Huron Healthcare and Texas Children’s Hospital (TCH) presented an educational session on the journey toward value-based care.
In the presentation, Huron Healthcare managing director, Larry Burnett, TCH Senior Vice President, Tabitha Rice, and TCH Assistant Vice President of nursing, Jackie Ward, shared valuable insights from their work together at TCH. Focusing on insights and results from TCH’s engagement with Huron Healthcare, the presentation includes:
• Opportunities and results at TCH in areas including care management, care progression, patient placement, and care variation.
• Keys to driving results, successful change, and integrated care delivery
• Steps for a sustainable approach
Lung cancer, which accounted for 1.8 million cases in 2012, is a serious issue in Asia. While it is primarily driven by smoking, non-smoking lung cancer is also growing due to pollution and oncogenic mutation.
Find out more about the severity of lung cancer in China, Taiwan, India, and Korea in our latest Social Innovation Playbook Series on SlideShare
Is the future of medicine chemo pills? In this webinar, we will delve into oral chemotherapy and explain why some patients are offered the option to receive cancer treatment in a pill form. We’ll discuss the advantages and challenges of this emerging treatment option and highlight the current therapies some patients receive. Join us to learn more about the future of treating colorectal cancer via pills.
Tonight’s speakers: Dr. Dan Sargent and Kim Ryan
Disclaimer: “This Report is not an official event of the 2012 Gastrointestinal Cancers Symposium. Not sponsored or endorsed by any of the cosponsoring organizations of the 2012 Gastrointestinal Cancers Symposium.”
Biomarkers and biomarker testing are changing the way some colorectal cancer is treated and knowing your biomarkers can help your doctors identify your best treatment options and help you in making well informed decisions about how your cancer will be treated allowing you to be your own best advocate.
Join in on this informative webinar with guest Dr. Christopher Lieu from the University of Colorado Cancer Center, as he discusses everything you need to know about biomarkers.
Every summer, the American Society for Clinical Oncology (ASCO) brings together internationally renowned cancer researchers, doctors and medical professionals to discover and discuss the latest in cancer research and patient care. This webinar, scheduled for June 19 2013 is presented by Dr. John Marshall, and will highlight the key colorectal cancer findings from the 2013 meeting and what these advances mean for you.
Poster presentation at the 2016 WORLD GASTROINTESTINAL SYMPOSIUM on tepotinib a selective inhibitor of c-MET by S. Faivre, J.-F. Blanc, P. Merle, A. Fasolo, A. Iacobellis, V. Grando, T. Decaens, J. Trojan, E. Villa, U. Stammberger, R. Bruns, E. Raymond
1Oncology Unit, Beaujon University Hospital, Clichy, France; 2Service d’hépato-gastroentérologie et d’oncologie digestive, Groupe Hospitalier Saint André, Bordeaux, France; 3Service d'Hépato-Gastro-Entérologie, Hôpital de la Croix Rousse, Lyon, France; 4Dipartimento di Oncologia Medica, Ospedale San Raffaele IRCSS, Milan, Italy; 5Servizio di Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy; 6Service Hépatologie, Hôpital Jean-Verdier, Bondy, France; 7Service d'hepato-gastro-enterologie, CHU de Grenoble - Hôpital Nord, Grenoble, France; 8Gastrointestinal Oncology, Goethe University Hospital, Frankfurt, Germany; 9Policlinico di Modena, Modena, Italy; 10Merck KGaA, Darmstadt, Germany
Dr Andrea Jorgensen - The future of innovation in atrial fibrillation and str...Innovation Agency
Presentation by Dr Andrea Jorgensen, Senior Lecturer - Biostatistics, University of Liverpool: Personalised Medicine in the treatment of AF at The future of innovation in AF and stroke prevention in the NWC, 27 June 2018, Haydock Park Racecourse
Dr. Murphy presents slides discussing general screening trends in the US, including how the US compares to other countries, different screening modalities, and differences in screening by:
-Age
-Gender
-Geography
-Race/Ethnicity
Looking to kick start your physical activity? Hoping to learn about how body movement can be a huge benefit for CRC patients and survivors? Curious about Climb for a Cure? Join this interactive webinar featuring Karia Coleman, MSK, personal trainer and athletic strength coach, and Fight CRC advocates as they discuss the importance, challenges, and joys of physical activity.
From bowel frequency, pain, and more, many colorectal cancer treatments lead to digestive side effects. Join this webinar with Dr. Cathy Eng to learn all about the digestive system, the side effects that are common due to CRC treatment, and how to manage those side effects.
Maine recently passed major colorectal cancer (CRC) policy at the state level. Join us to listen to their story and learn what worked well for CRC state advocacy!
Indiana just passed major colorectal cancer (CRC) policy this year. Join us to listen to their story and learn what worked well for CRC advocacy in Indiana!
Kentucky was one of the first states in the US to pass major colorectal cancer (CRC) policy. Join us to listen to their story and learn what worked well for CRC state advocacy!
Join Fight CRC in a webinar about biomarkers. In this session, Dr. Chris Lieu will focus the discussion on the NTRK biomarker, in addition to ctDNA, and Next-Generation Sequencing.
Join us as Eden Stotsky-Himelfarb, BSN, RN from Johns Hopkins Medicine discusses how to manage after a colorectal cancer diagnosis. In this session, she will cover understanding diagnoses, shared decision making, managing mental health, talking to family and colleagues, and more.
Some colorectal cancer treatments lead to side effects of the skin. In this webinar, Dr. Nicole LeBoeuf will discuss these specific side effects. She will talk about why they occur, how to prepare for them, and how to manage them.
Hear about the latest breaking colorectal cancer research! Fight CRC will be joined by Dr. Axel Grothey who will spend the hour detailing the research presented at the 2020 Gastrointestinal (GI) Cancers Symposium hosted by the American Society of Clinical Oncology.
Anticipating the end of life and making decisions about medical care at this time can be difficult and distressing for people with cancer and their loved ones. However, it is incredibly important to plan for the transition to end-of-life care.
In this webinar, we will discuss questions to ask when considering an end to curative treatment, what to expect with hospice and end-of-life care, a new medical care team, advance directives and healthcare proxies, options for pain, the role of caregivers and loved ones, and more.
In this webinar, Dr. Angela Nicholas, Dr. Chris Heery, and Wenora Johnson discuss all things clinical trials. Dr. Nicholas, a family practitioner and caregiver to her late husband, John MacCleod will dive into her experience searching for clinical trials along with advice to those currently searching, or planning on searching in the future. Dr. Heery, Chief Medical Officer for Precision Biosciences will spend time dispelling myths around clinical trials and challenges to enrollment, and Wenora Johnson, a stage III colon cancer survivor will describe the process and her point of view curating trials in the Fight CRC trial finder.
In this webinar, Dr. Popp will discuss everything you need to know about palliative care! This is an important webinar for colorectal cancer patients and their loved ones.
eeling worn out and exhausted all the time? You may be experiencing cancer-related fatigue. Tune in to this webinar to learn what cancer-related fatigue is, how to spot it, and how to manage it.
In this webinar, Dr. Azad discusses colorectal cancer recurrence. She addresses things to do to help reduce the risk of recurrence, in addition to what steps should be taken if colon or rectal cancer returns.
Join Fight CRC and Dr. Scott Kopetz to learn about the latest breaking colorectal cancer research from the American Society of Clinical Oncology 2019 Annual Conference.
May 2019 – What You Need to Know About Chemotherapy Induced Neuropathy WebinarFight Colorectal Cancer
Neuropathy is a common side effect for colorectal cancer patients. It is a side effect that can be incredibly challenging to manage, and can affect daily living. Join this informative webinar to learn all about neuropathy—why it happens, how to prepare for it, and methods to try and reduce its effects. This is an important webinar for all survivors and patients! Dana will speak from both the medical professional and patient angle, as she is a colon cancer survivor herself!
A cancer diagnosis and cancer treatment can be traumatic. An experience with cancer can lead to serious psychological distress that should be addressed. In this webinar, Schuyler Cunningham, Clinical Social Worker, talks about what trauma is, how to identify it, and what steps to take next.
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Pathways and targets how might these affect my treatment decisions gail eckhardt webinar
1. Welcome!
Pathways and Targets:
How do these affect my treatment
options?
Part of Fight Colorectal Cancer’s Monthly Patient Webinar Series
Our webinar will begin shortly
www.FightColorectalCancer.org
877-427-2111
2. Fight Colorectal Cancer
1. Tonight’s speaker: Dr. Gail Eckhardt, MD
2. Archived webinars: Link.FightCRC.org/Webinars
3. Follow up survey to come via email. Get a free Blue Star of
Hope pin when you tell us how we did tonight.
4. Ask a question in the panel on the right side of your screen and
look for hyperlinks during throughout the presentation.
5. Or call the Fight Colorectal Cancer Answer Line at 877-427-2111
www.FightColorectalCancer.org
877-427-2111
3. Fight Colorectal Cancer
Disclaimer
The information and services provided by Fight Colorectal
Cancer are for general informational purposes only.
The information and services are not intended to be substitutes
for professional medical advice, diagnosis, or treatment.
If you are ill, or suspect that you are ill, see a doctor
immediately. In an emergency, call 911 or go to the nearest
emergency room.
Fight Colorectal Cancer never recommends or endorses any
specific physicians, products or treatments for any condition.
www.FightColorectalCancer.org
877-427-2111
4. Fight Colorectal Cancer
Up coming webinars
Peripheral Neuropathy: Will it ever go away?
Problems, Causes, Solutions
October 16, 2013
8 - 9:30pm EDT
Advances in Surgical Treatments for Colon and
Rectal Cancer Patients
November 20, 2013
8 - 9:30pm EDT
6. Pathways and Targets: How do
these affect my treatment
options?
S. Gail Eckhardt, M.D.
University of Colorado Cancer Center
7. CRC: What Have We Learned?
• Patient selective trials are needed earlier in order to
avoid thousands of patients being treated with
ineffective agents (EGFR Ab/KRAS)
• Indiscriminant addition of biological agents to
adjuvant therapy is not warranted
(bevacizumab/cetuximab)
• Dual biological combinations in unselected patients
may lead to more toxicity with little benefit
(bevacizumab + cetuximab)
9. • Solid tumors cannot grow beyond 1-2 mm3 without an increase in blood
supply via new vessel formation
• Angiogenesis is thus required for tumor growth and metastasis
• Inhibition of tumor angiogenesis leads to tumor cell growth arrest, death
of tumor cells, and in some cases, tumor regression
Tumor angiogenesis is
stimulated…
New vessels then facilitate
tumor growth
Slide Courtesy of Novartis Oncology
Targeting Angiogenesis in CRC
10. VEGF: A Central Mediator of
Angiogenesis
Binding and activation
of VEGF receptor
Environmental factors
(hypoxia, pH)
Growth factors,
hormones
(EGF, bFGF, PDGF,
IGF-1, IL-1 , IL-6, estrogen)
Genes involved in
tumorigenesis
(p53, p73, src, ras, vHL,
bcr-abl)
P
P
P
P
ANGIOGENESIS
ProliferationSurvival Migration
Endothelial cell
activation
VEGF
1. Dvorak. J Clin Oncol. 2002;20:4368.
2. Ferrara et al. Nat Med. 2003;9:669.
3. Ebos et al. Mol Cancer Res. 2002;1:89.
12. Pivotal Randomized Phase III Trial of 813 Advanced CRC
Patients Comparing IFL Regimen +/- Bevacizumab
Primary Endpoint: Survival
Previously untreated
pts with metastatic
colorectal cancer
Arm A: IFL + Bevacizumab
Arm B: IFL + Placebo
IFL = Irinotecan / 5-FU / Leucovorin
Hurwitz et al, N Engl J Med.
2004 Jun 3;350(23):2335-42.
13. p<.001
Results: Bevacizumab added to IFL significantly
improved overall survival by > 4 months
Hurwitz et al, N Engl J Med. 2004 Jun 3;350(23):2335-42.
Copyright Mass Med Soc
14. VEGFR Tyrosine Kinase Inhibitors in CRC:
Over 10,000 CRC Patients Treated on Negative Trials!
Agent AKA mCRC Trials CRC Patients
Cediranib AZD2171 2 Phase III 3,194
Semaxinib SU5416 2 Phase III 2,084
Vatalanib PTK787 2 Phase III 2,050
Sunitinib SU11248 Phase III 1,623
Brivanib BMS-582664 Phase III 926
Sorafenib BAY 43-9006 Phase IIB 814
Vandetanib ZD6474 Phase IIB 356
Axitinib AG-013736 Phase IIB 299
Linifanib ABT-869 Phase IIB 147
Vargateg BIBF 1120 Phase II 166
Tivozanib AV-951 Phase II 80
Motesanib AMG-706 Phase IB 148
Pazopanib GW786034 Phase IB 94
Clinicaltrials.gov; Slide courtesy of Scott Kopetz
15. Mode of Action of Regorafenib
• Regorafenib inhibits multiple cell-
signaling kinases:
– Angiogenic
• VEGFR1–3, TIE2
– Stromal
• PDGFR-β, FGFR
– Oncogenic
• KIT, PDGFR, RET
• T1/2 in man: approx. 26-28 hrs
– Two major metabolites (M2,
M5) are pharmacologically
active
Wilhelm SM et al. Int J Cancer 2011
17. Regorafenib:
Overall survival (primary endpoint)
Primary endpoint met prespecified stopping criteria at interim analysis
(1-sided p<0.009279 at approximately 74% of events required for final
analysis)
1.00
0.50
0.25
0
0.75
200100500 150 300250 400350 450
Days from randomization
Survivaldistributionfunction
Placebo N=255
Regorafenib N=505
Median 6.4 mos 5.0 mos
95% CI 5.9–7.3 4.4–5.8
Hazard ratio: 0.77 (95% CI: 0.64–0.94)
1-sided p-value: 0.0052
Regorafenib Placebo
Grothey et al, ASCO GI 2012
42 days!
18. Aflibercept
Another Approach to Targeting Angiogenesis
• Soluble fusion protein
• Consists of portions of the extracellular domains of
human VEGFR1 and VEGFR2 fused to a human IgG1
Fc portion
• Binds all VEGF-A isoforms, VEGF-B, and PlGF
• High affinity: Binds VEGF-A and PlGF more tightly
than native receptors
• Half-life ~ 17 days
Van Cutsem et al, 2011.
20. “VELOUR” trial
Similar Combination Approach as Bev
- Aflibercept (VEGF Trap) in colorectal cancer
- Multiple centers in Australia, China, Europe, Japan, and
North America
mCRC after
failure of an
oxaliplatin-based
regimen
N=1200
Placebo
+ FOLFIRI
(n=605)
R
Aflibercept 4 mg/kg IV
+ FOLFIRI
(n=611)
Primary Endpoint: Overall Survival (OS)
1:1
Note: 30% had received prior bevacizumab
Van Cutsem et al, 2011.
(FOLFIRI= infusional 5FU/IRI/LV)
22. “VELOUR” trial: Overall Survival
Cut-off date = February 7, 2011; Median follow-up = 22.28 mos
Van Cutsem et al, 2011.
6 weeks longer OS
Not compared to bevacizumab
23. Issues Regarding Angiogenesis Inhibitors
– Most medical oncologists believe that utilization of AIs
is relevant throughout the course of advanced CRC
(when risks are acceptable)
– Bevacizumab can be used with chemotherapy and the
reason aflibercept is not being routinely used is related
to unfamiliarity and concerns regarding the toxicity
data
– For some reason, although regorafenib was active in
refractory patients, drugs that are similar have not
worked with chemotherapy
– Among those involved in clinical research (like me), we
are worried that patients will get regorafenib rather
than be offered a clinical trial
24. Can Biomarkers Help Us Select the
Patients Most Likely to Benefit from
Targeted Therapies ?
25. Biomarker = Toxicity (mechanism based)
Biological effect
Efficacy
Pharmacodynamic biomarker: Associated with drug
effect
Example: skin rash with EGFR inhibitor, or inhibition of p-ERK with MEK
inhibitor
Predictive biomarker: Predicts outcome to therapy
Example: Her2/Neu amplification by FISH for trastuzumab
Prognostic biomarker: Associated with outcome,
independent of therapy
Example: VEGF expression
Biomarkers: Introduction
26. Biomarkers for Bevacizumab in CRC
• Although there are biomarkers associated with the PD
effects of bevacizumab, to date to no predictive
biomarkers have been identified
• This is likely due to the complex interaction of the
tumor and microenvironment
• Studies are ongoing to determine whether the PD
biomarkers such as high blood pressure and MRI can
be used to identify patients deriving clinical benefit
27. EGFR Antibodies Target Tumor Cell-Bound EGFR
Extracellular
Intracellular
Ligand
EGF-R
PI3K
Akt
Raf
MEK
MAPK
Cell Motility
MetastasisAngiogenesis
Proliferation
Cell survival
DNA
PTEN
Ras
Slide courtesy of Axel Grothey
Targeting the EGFR in CRC
30. Did staining for EGFR matter? NO!
Courtesy of DakoCytomation, 2004
21% 25%
23%
Response Rates
31. EGFR Signaling Cascade and KRAS
Akt
SOS
FOS Myc
P13K
FKHR
mTOR
PTEN
MEK 1/2
MAPK
BAD
GSK-3
Shc
Grb-2
Ras
Raf
Jun
p27
Cyclin D-1
Ligand
Signal
Adapters
and Enzymes
Signal
Cascade
EGFR dimer
Transcription
Factors
STAT
Inhibitors upstream may be
ineffective
Karapetis WGIC 2008
32. Randomized Trial Results
Median PFS (Cetux- or Pmab- containing arms)
Study Treatment
Total Pts
MT WT
Amado
2008
P versus BSC
(3rd line)
427
7.4 wks
HR 0.99
12.3 wks
HR 0.45
Karapetis
2008
C versus BSC
(no X-over)
394 1.9 mos
3.7 mos
HR 0.40
Van Cutsem
2008
FOLFIRI +/- C
(1st line)
540
7.6 mos
HR 1.07
9.9 mos
HR 0.68
Bokemeyer
2008
FOLFOX +/- C
(1st line)
233
5.5 mos
HR 1.83
7.7 mos
HR 0.57
C = cetuximab; P = panitumumab; BSC = best supportive care
33. Amgen “408” Trial
This trial was important because it had a
placebo arm
Patients had to be “EGFR positive,” defined as >1% tumor
cells staining by IHC
Pretreated with 5-FU, oxaliplatin, irinotecan
Previously treated
metastatic
colorectal cancer
N=463
Panitumumab 6 mg/kg
Q2 weeks
Best Supportive Care
OptionalCrossover
Van Cutsem et al. J Clin Oncol; 25(13):1658-1664 2007
34. PFS by treatment overall
Van Cutsem et al. J Clin Oncol; 25(13):1658-1664 2007
Resulted in FDA
approval of
panitumumab
for use in 3rd
line setting
35. Amado, R. G. et al. J Clin Oncol; 26:1626-1634 2008
PFS by treatment within KRAS groups
Note: The BSC arms look similar indicating lack of impact on prognosis
KRAS MT
KRAS WT
BSC
BSC
36. KRAS and Panitumumab
Waterfall plot shows
responses (tumor
shrinkage) were
confined to Ras WT
patients
Mut WT
Amado, R. G. et al. J Clin Oncol; 26:1626-1634 2008
38. M Peeters et al, Cancer, 2009
More severe skin toxicity
and associated
symptoms led to
prolonged survival in this
subset analysis
Grade 2+ skin toxicity
Greater skin toxicity
symptoms
Skin Rash: Maybe necessary but not
sufficient for antitumor activity
39. Summary and Lessons Learned with EGFR Inhibitors in CRC
• EGFR-targeted antibodies have very modest single-agent activity
in refractory CRC but appear to improve responses to
chemotherapy
• Biomarker studies have demonstrated that benefit is restricted
to KRAS WT patients
• Surprisingly, no benefit was observed in the adjuvant studies
• Ongoing questions remain regarding the extent to which
immune mechanisms contribute to antitumor effects and how
to integrate skin rash data in dosing decisions
• The EGFR TKIs (oral drugs) have not exhibited activity in CRC
40. What About the Combination of
Biologics- is More Better????
41. PACCE Trial:
Randomized phase III trial of 1000 patients comparing
chemo/Bev with or without panitumumab
Previously
untreated
metastatic
colorectal cancer
N=1000
5-FU/Oxali/Bev
N=800
5-FU/Irino/Bev
N=200
Hecht, World GI 2007
+ panitumumab
+ panitumumab
(alone)
(alone)
42. PACCE Trial
Progression-Free Survival
Hecht, World GI 2007
Months
413 267 92 21 3
410 298 96 21 1
0 5 10 15 20
Pmab+bev/Ox-CT N
bev/Ox-CT N
Patients at risk:
# PFS events
(%)
Median
(95%CI), mos
206 (50) 9.0 (8.5-10.4)
172 (42) 10.5 (9.7-11.6)
Pmab+bev/Ox-CT
Bev/Ox-CT
HR= 1.29 (95% CI: 1.05-1.58)
ProportionProgression-Free
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
ITT set
Control group did better!
44. Conclusions
• Novel biological agents targeting the EGFR and VEGF pathways
have extended survival and provided new options for CRC
patients with advanced disease
• Unfortunately, these results have not translated to adjuvant
therapy and the reasons for this are not well understood
• Biomarkers have been instrumental in further defining a
potentially responsive patient population
• These results, along with the issues of combining “double
biologics” in unselected patients, are driving the field forward
towards personalized therapy and more rational combinations
• Despite the advances in therapy, more effective agents are
needed and luckily drug development is robust, but very
dependent on clinical trials
46. Fight Colorectal Cancer
CONTACT US
Fight Colorectal Cancer
1414 Prince Street, Suite 204
Alexandria, VA 22314
(703) 548-1225
Toll-Free Answer Line: 1-877-427-2111
www.FightColorectalCancer.org
Email us: Info@FightColorectalCancer.org