Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
The Changing Role of PARP Inhibitors in the Treatment of Ovarian Cancerbkling
In recent years, researchers have been looking into using a class of drugs called PARP inhibitors to prevent the progression and recurrence of ovarian cancer. Dr. Kathleen Moore of Stephenson Cancer Center, Principal Investigator of the SOLO-1 trial, explains how the results of this trial may affect ovarian cancer patients and where research on ovarian cancer treatment is headed next.
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
The Changing Role of PARP Inhibitors in the Treatment of Ovarian Cancerbkling
In recent years, researchers have been looking into using a class of drugs called PARP inhibitors to prevent the progression and recurrence of ovarian cancer. Dr. Kathleen Moore of Stephenson Cancer Center, Principal Investigator of the SOLO-1 trial, explains how the results of this trial may affect ovarian cancer patients and where research on ovarian cancer treatment is headed next.
Please share this video with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
In this webinar:
● Understanding colorectal and anal cancer, including symptoms, risk factors
● Treatment options, including chemotherapy, radiation and biologics
● Preventing colorectal and anal cancer
View the video: https://youtu.be/q0z8N1_L-JQ
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Expanding treatment platform in m crc bayer - asyut 2018Mohamed Abdulla
Describes the different therapeutic approach to patients with metastatic colorectal cancer in the 3rd subsequent treatment line with especial emphasis on the role of regorafenib and how to manipulate the adverse events while not compromise the outcome.
Cette présentation faite le 27 Avril 2017 à l'Hôpital Saint Joseph organisée par le Dr Vincent de Parades fait le point sur les nouvelles approches multidisciplinaires dans la prise en charge des cancers colorectaux en insistant sur la prise en charge de la maladie métastatique hépatique et de la carcinome péritonéale pour terminer sur les nouvelles approches par immunothérapie. Cette EPU a connu un large succès d'audience avec plus de 60 participants. Merci à toutes et tous.
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.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Prostate cancer the androgenic fortified dogmaMohamed Abdulla
It describes the androgenic nature of prostate cancer and the androgenic axis should be tackled in all phases of prostate cancer. Also a special emphasis on recent data on management of metastatic hormone sensitive prostate cancer.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. mCRC:
The Paradigm of Sequence or
Still Maximum Exposure?
Evidence from RCT
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
Asyut Annual Meeting
Merck Serono Lecture
Luxor: 22/02/2017
2. Member of Advisory Board, Consultant, and Speaker for:
• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer, Mundipharma, MSD
Speaker Disclosures:
3. Colon Cancer:
Basic Facts & Figures:
• 2nd & 3rd most common cancers in females and males.
• 9% of cancer related deaths.
• 90% occurring around the age of 40 – 50 years.
• OAS for entire patients = 65%.
• Metastatic disease: 5-year OAS = 10%.
• Organ limited metastatic disease (Metastatectomy):
5-year OAS > 40%
• Median survival of metastatic disease > 35 months.
• Improved OAS with exposure to all available drugs.
• Unified global treatment algorhytm is still controversial.
4. Median OS
Months
1980s 1990s 2000s
BSC 5-FU
Irinotecan1
Capecitabine2
Oxaliplatin3
Bevacizumab4
Cetuximab5,6BSC
Panitumumab
7 Aflibercept8
Regorafenib
9
30
25
20
15
10
5
0
1. Cunningham D, et al. Lancet. 1998;352(9138):1413-1418. 2. Van Cutsem E, et al. Br J Cancer.
2004;90(6):1190-1197. 3. Rothenberg M, et al. J Clin Oncol. 2003;21(11):2059-2069.
4. Hurwitz H, et al. N Engl J Med. 2004;350(23):2335-2342. 5. Cunningham D, et al. N Engl J Med.
2004;351(4):337-345. 6. Van Cutsem E, et al. N Engl J Med. 2009;360(14):1408-1417.
7. Van Cutsem E, et al. J Clin Oncol. 2007;25(13):1658-6164. 8. Van Cutsem E et al. J Clin Oncol.
2012;30(28):3499-3506. 9. Grothey A, et al. Lancet. 2013;381(9863):303-312.
mCRC:
Improved Survival Over Time:
5. Choice of Systemic Therapy:
Old Dogma:
5-Fu/LV
Capecitabine
Oxaliplatin
Irinotecan
Bevacizumab
Cetuximab
Panitumumab
Aflibercept
Regrafinib
Ramucirumab
TAS 102
Survival Improvement
Treatment
Lines &
Combinations
6. mCRC:
Can we do better?
Treatment
INTENTION
Organ Confined
Disease
NAT:
Resectable
Or Convertible
Resection
for Cure
Progressive
Metastatic
Palliative
Treatment
OAS
QoL
7. Can We Do Better?
• MDT
• Predictive Markers K-RAS Assessment All RAS
Assessment SEQUENCE SMART & STRATEGIC
8. Daily Treatment Scenarios:
Exposure:
• Advancing Cancer
Chronic Disease.
• Survival All Active
Agents.
• Sequence isn’t important
Sequence:
• Predictive Markers
• Upfront Massive Attack.
• Late still wining cards
• Survival Improvement is modest in 2n & 3rd Lines.
• Losing an Active Agent Out of Upfront Treatment.
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No. 2, 81-90 a 2015
9. ORR, %*
PFS, months*
Importance of 1st line treatment
decision
1st line1-4 2nd line5–7 3rd line8,9
1‡ – 22†
2‡ – 4†
38‡ – 69
9‡ – 13
10† – 41
4† – 9†
Treatment is most effective in the 1st line1–9
Determining RAS status at diagnosis is crucial for maximizing patient
outcomes and planning the course of treatment
1. Saltz LB, et al. J Clin Oncol 2008;26:2013–2019; 2. Lenz HJ, et al. ESMO 2014
(Abstract No. 501O); 3. Pericay C, et al. WCGC 2012 (Abstract No. O-0024);
4. Karthaus M, et al. ECC 2013 (Abstract No. 2262); 5. Langer C, et al. ESMO
2008 (Abstract No. 385P); 6. Peeters M, et al. ASCO GI 2014 (Abstract No.
LBA387);
7. Cohn A, et al. ASCO 2013 (Abstract No. 3616); 8. Grothey A, et al. Lancet
2013;381:303–312; 9. Price TJ, et al. Lancet Oncol 2014;15:569–579
*Range of results for the targeted
treatment arms of key Phase II/III
trials (RAS wt except where
indicated;
†KRAS exon 2 wt; ‡unselected)
11. KRAS WT: Impact of All RAS Testing:
1. PFS
Sorich et al. Annals of Oncology 26: 13–21, 2015
12. KRAS WT: Impact of All RAS Testing:
2. OAS
Sorich et al. Annals of Oncology 26: 13–21, 2015
13. CRYSTAL5
COIN3
PRIME4
NORDICVII2
CO.179
4088
N01471
PFS for EGFR inhibitors improves across lines of
therapy in KRAS dliw-stnetiap epyt:
Hazardratio
1. Alberts, et al. JAMA 2012;2OCJ .la te ,tievT .2012;3tecnaL .la te ,nahguaM .2011
4. Douillard, et al. ASCO 2011;5OCJ .la te ,mestuC naV .2011;6OMSE .la te ,regnaL .2008
7. Sobrero, et al. ASCO GI 2012;8OCJ .la te ,odamA .2008;9MJEN .la te ,stieparaK .2008
First line Second line Salvage
(single agent)
Adjuvant
1.2
1.0
0.8
0.6
0.4
0.2
0
Study1817
EPIC6
Albert Sobrero , WCGIC 2012
14. First Head-to-Head Comparisons of First-Line
Bevacizumab Versus EGFR Inhibitors in KRAS WT
mCRC
1. Schwartzberg LS, et al. J Clin Oncol. 2014;32(21):2240-2247. 2. Heinemann V, et al. Lancet Oncol. 2014;15(10):1065-1075.
3. Venook A, et al. J Clin Oncol. 2014;32(Suppl): Abstract LBA3.
PEAK1
Phase II
Untreated –
Unresectable mCRC
N = 285
Bevacizumab + mFOLFOX6
Panitumumab + mFOLFOX6
FIRE-32
Phase III
Untreated mCRC
N = 592
Bevacizumab + FOLFIRI
Cetuximab + FOLFIRI
CALGB-804053
Phase III
Untreated mCRC
N = 1200
Bevacizumab +
FOLFIRI or FOLFOX
Cetuximab
+ FOLFIRI or FOLFOX
No Hypothesis
OAS
ORR
DP
15. FIRE-3 Trial: FOLFIRI + Either Cetuximab or
Bevacizumab in KRAS WT mCRC
Heinemann V, et al. Lancet Oncol. 2014;15(10):1065-1075.
HR 0.77
P .011
Parameter Chemo + CET Chemo + Bev P
ORR (%) 62 58 .183
PFS (ms) 10 10.3 .547
OAS Dif.
= 8.5 ms
16. CALGB/SWOG 80405: Overall Survival
Arm N (Events)
OS (m)
Median
95% CI
Chemo +
Cetux 578 (375) 29.9 27.0-32.9
Chemo + Bev 559 (371) 29.0 25.7-31.2
P=0.34
HR 0.925 (0.78-1.09)
17. CALGB/SWOG 80405: Progression-Free Survival
(Investigator Determined)
Arm N (Events)
PFS (m)
Median
95% CI
Chemo + Bev 559 (498) 10.8 9.7-11.4
Chemo + Cetux 578 (499) 10.4 9.6-11.3
P=0.55
HR 1.04 (0.91 -1.17)
29. Lancet Oncol 2016; 17: 1426–34
Which Treatment Line First?
Better Insight:
30. Correlation between ETS and increased OS has been
consistently observed in 1st line Phase III clinical
trials
• 1. Piessevaux H, et al. J Clin Oncol 2013;31:3764–3775;
2. Stintzing S, et al. ESMO 2014 (Abstract No. LBA11);
3. Douillard JY, et al. Eur J Cancer 2015;51:1231–1242;
4. Cremolini C, et al. Ann Oncol 2015;26:1188–1194;
5. Erbitux SmPC June/2014;
6. Heinemann V, et al. Lancet Oncol 2014;15:1065–1075.
*KRAS exon 2 wt population; Cetuximab is approved in patients with RAS wt mCRC.6 Cetuximab is not indicated for the
treatment of patients with mCRC whose tumors have RAS mutations or for whom RAS tumor status is unknown.5
**FIRE-3 did not meet its primary endpoint of significantly improving ORR in patients with KRAS (exon 2) wt mCRC
based on investigators’ read.6
†Not including the first four months after randomization.
Trial
Biomarker
status
Treatment regimen
(n)
OS, months ∆OS,
mont
hs
ETS
<20%
ETS ≥20%
CRYST
AL1
KRAS exon
2 wt*
FOLFIRI + cetuximab (n=299) 18.6 30.0 11.4
FOLFIRI (n=332) 18.6 24.1 5.5
FIRE-
3**2 RAS wt
FOLFIRI + cetuximab (n=157) 20.5 38.3 17.8
FOLFIRI + bevacizumab
(n=173)
21.2 31.9 10.7
PRIME
3 RAS wt
FOLFOX4 + panitumumab
(n=219)
12.6 32.5 19.9
FOLFOX4 (n=221) 15.2 26.0 10.8
TRIBE4 Unselected
FOLFOXIRI + bevacizumab/
FOLFIRI + bevacizumab
(n=407)
21.9† 31.9† 10.0
31. Inducing ETS with Cetuximab correlates with
symptoms relief and QoL
1. Griebsch I, et al. ASCO GI 2011 (Abstract No. 3626)
32. 16
14
12
10
8
6
4
2
0
13,2
2,,00
5,1
14
12
10
8
6
4
2
0
KRAS wt –
Liver-limited disease
cohort
CRYSTAL
7,3
3,1
Patients,%
OPUS
Patients,%
KRAS wt-
Liver-limited disease
cohort
16.0
KRAS wt
P = .22 †KRAS wt
P = .027 †
4,3
Van Cutsem E, et al. J Clin Oncol. 2011;29(4S): Abstract 472.
*Fisher’s exact test;
†Cochran-Mantel-Haenszel test
P = .15*
P = .35*
5,6
R0 RESECTIONS IN RANDOMIZED TRIALS WITH CETUXIMAB
FOLFIRI ERBITUX FOLFIRI ERBITUX FOLFOX4 ERBITUX FOLFOX4 ERBITUX
N = 350 + FOLFIRI N = 72 + FOLFIRI N = 97 + FOLFOX4 N = 23 + FOLFOX4
N = 316 N = 68 N = 82 N = 25
33. 1. Folprecht G et al. Lancet Oncol 2010; 11(1): 38-47.
Higher Resection Rates correlates with Prolonged OS and PFS
34. Phase III TAILOR study:
open-label, randomized ,1st line FOLFOX-4 ± Erbitux in
patients with RAS wild-type metastatic colorectal cancer (RAS
wt mCRC)
3
First prospective Phase III analysis to assess the efficacy and safety of Erbitux plus
FOLFOX versus FOLFOX alone as 1st line therapy in RAS wt mCRC
Endpoints
• Primary:
PFS
• Key secondary:
OS, ORR,
safety/tolerability
1st line,
RAS wt
mCRC
R
1:
1
Arm A:
Erbitux +
FOLFOX-4
Arm B:
FOLFOX-4
alone
Treatment
until
progressive
disease or
unacceptable
toxicity*
IRC, independent review committee; HR, hazard ratio; OS, overall survival; ORR, overall response rate
*In the case of non-PD treatment discontinuation, tumor assessment was to be continued
FOLFOX-4:
• Oxaliplatin 85 mg/m2 Day 1, every 2 weeks
• Folinic acid 200 mg/m2 Day 1 and Day 2, every 2 weeks
• 5-FU 400 mg/m2 bolus, then 22h continuous infusion of 600 mg/m2/day Day 1
and Day 2, every 2 weeks
Erbitux:
• 400 mg/m2 Day 1, then 250 mg/m2/week
Qin S, et al. WCGC 2016 (Abstract no. O-025)
35. 35
GORTEC 2007-021
TAILOR
Confirms Erbitux as a Standard of care
for all patients with RAS wt mCRC, with
consistent benefit in combination with
standard CT regimens
PFS: 9.2 vs 7.4 months1
HR: 0.69
p=0.004
• ORR: 61.1% vs 39.5%1
OR: 2.41
p=<0.001
• OS: 20.7 vs 17.8 months1
HR: 0.76
p=0.02
SOC, standard of care; CT, chemotherapy; PFS, progression-free
survival; HR, hazard ratio; OS, overall survival; ORR, overall
response rate
6
31% decrease in the risk
of disease progression1
• 24% reduction in the
risk of death1
• 61% ORR is consistent
with previous studies2,3
1. Qin S, et al. WCGC 2016 (Abstract no. O-025)
2. Van Cutsem E, et al. J Clin Oncol 2015;33:692–700;
3. Bokemeyer C et al. Eur J Cancer 2015;51:1243–1252
Significant benefit with Erbitux + FOLFOX versus FOLFOX alone
across all efficacy endpoints1
37. 37
FIRE-3
No difference in outcomes
between arms in right-sided
tumors, but conclusions are
limited by small sample size &
imbalances
38.3
38. 38
CRYSTAL
No significant difference in
outcomes between arms in
right-sided tumors, but
conclusions are limited by small
sample size
Numerical
increase in ORR
compared with
CT alone
In RS, patients in the Erbitux
arm had poorer PS, larger
tumors, and more frequent
prior adjuvant therapy,
compared with CT alone
28.7
39. 39
CALGB/SWOG
80405
Longer PFS with
bevacizumab vs Erbitux, but
no difference in OS between
arms, in right-sided tumors;
conclusions limited by small
sample size
Data for patients with right-sided tumors are
inconclusive due to:
• Small patient numbers
• Unreported baseline characteristics,
treatment dose, treatment duration and
subsequent therapies
39.3
40. ~30% of patients
40
Conclusion
~70% of patients
Median OS
>38 months!
• Over 10 months more than bev + CT
(FIRE-3)
• 7 months more than bev + CT (CALGB
80405)
• 7 month more than CT (crystal)
Bad prognosis
regardless of
therapy
Small sample size ,
premature data
LEFT RIGHT
41. Anti-EGFR agents
1. Erbitux SmPC June/2014;
2. Imai K, Takaoka A. Nat Rev Cancer 2006;6:714–727;
3. Vectibix SmPC February/2015.
Human constant
domains
Mouse
variable
domains
Human constant and
variable domains
Cetuximab1,2 Panitumumab2,3
Chimeric monoclonal
IgG1 antibody
Fully human monoclonal
IgG2 antibody
Differences in molecular structure
Potent ADCC Less ADCC
42. Take Home Message:
• Better insight to decide for first line treatment.
• Growing evidence of 1st line Anti-EGFR MCA as SOC in All-
RAS wild type patients (Resection or OAS).
• Availability of 2nd line data from major RCT emphasized the
survival advantage of 1st line Anti-EGFR based combination
therapy.
• Emphasizing ETS as an endpoint to predict Survival,
Resectability and Symptom Relief.
• Data for tumor location needs more validation, with
retrospective data favoring anti-EGFR for left sided tumors.
• Immunogenic response to Cetuximab needs to be
highlighted in the era of immunotherapy.
Right time:
Determining RAS status at diagnosis is crucial to selecting the optimal 1st line treatment for individual patients with mCRC and planning the course of treatment
Treatment is most effective in 1st line1–9
PFS and ORR decrease across the treatment continuum1–9
The proportion of patients receiving therapy diminishes with subsequent lines10,11
Only ~50% of patients receive 2nd line therapy10,11
Testing for RAS (and other future biomarker) status at diagnosis gives patients the opportunity to receive the best treatment for them