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.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
Therapeutic prospects in Cancer Immunotherapy.
Interleukins for Renal Cell Carcinoma.
BCG for Bladder Cancer.
Vaccination Strategies: Oncolytic virus for melanoma, Dendritic Cell therapy for CA Prostate.
Immune Checkpoint inhibitors. PD1 and PD L1 inhibitors.
Adoptive Cell Therpay. CAR T Cell Therapy
Clinical efficacy. Costs.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
Therapeutic prospects in Cancer Immunotherapy.
Interleukins for Renal Cell Carcinoma.
BCG for Bladder Cancer.
Vaccination Strategies: Oncolytic virus for melanoma, Dendritic Cell therapy for CA Prostate.
Immune Checkpoint inhibitors. PD1 and PD L1 inhibitors.
Adoptive Cell Therpay. CAR T Cell Therapy
Clinical efficacy. Costs.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
A detailed ppt about cancer immunotherapy.
includes:-
Immunosurveillance and Immunoediting
Dentritic cell vaccines
Antibody therapy
Combined therapy
immune blockades
Cytokine therapy
T cell therapy
Include latest research finding about therapy.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
In this webinar:
Dr. Michele Ardolino, Assistant Professor at the University of Ottawa, Department of Biochemistry, Microbiology, and Immunology and Scientist Ottawa Hospital Research Institute, discusses: The body has a phenomenal weapon to fight infections and cancer: the immune system. This seminar focuses on how the immune system recognizes and shapes cancer and on how research in tumor immunology led to the development of life-saving and revolutionizing immuno-therapies.
The webinar is followed by a question & answer session.
View the video:
https://youtu.be/-a7DfHT8dU8
To learn more about CCSN, visit us at survivornet.ca
Follow CCSN on social media:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurv...
Instagram: https://www.instagram.com/survivornet...
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Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Presented by Matthew Rioth, MD, MS. Presented at the 2018 Eyes on a Cure: Patient & Caregiver Symposium, hosted by the Melanoma Research Foundation's CURE OM initiative.
A detailed ppt about cancer immunotherapy.
includes:-
Immunosurveillance and Immunoediting
Dentritic cell vaccines
Antibody therapy
Combined therapy
immune blockades
Cytokine therapy
T cell therapy
Include latest research finding about therapy.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
In this webinar:
Dr. Michele Ardolino, Assistant Professor at the University of Ottawa, Department of Biochemistry, Microbiology, and Immunology and Scientist Ottawa Hospital Research Institute, discusses: The body has a phenomenal weapon to fight infections and cancer: the immune system. This seminar focuses on how the immune system recognizes and shapes cancer and on how research in tumor immunology led to the development of life-saving and revolutionizing immuno-therapies.
The webinar is followed by a question & answer session.
View the video:
https://youtu.be/-a7DfHT8dU8
To learn more about CCSN, visit us at survivornet.ca
Follow CCSN on social media:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurv...
Instagram: https://www.instagram.com/survivornet...
Pinterest - https://www.pinterest.com/survivornet...
Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Presented by Matthew Rioth, MD, MS. Presented at the 2018 Eyes on a Cure: Patient & Caregiver Symposium, hosted by the Melanoma Research Foundation's CURE OM initiative.
Chair, David M. O'Malley, MD, Ana Oaknin, MD, PhD, and Matthew A. Powell, MD, prepared useful Practice Aids pertaining to endometrial cancer for this CME/MOC/AAPA activity titled “Endometrial Cancer Care in the Age of Immunotherapy: Translating Clinical Evidence Into Meaningful Improvements in Patient Outcomes Across the Disease Continuum.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40bmalK. CME/MOC/AAPA credit will be available until July 3, 2024.
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
Ebmt 2018 gps in mm koehne et al_with suppl slides_final_final_1.1.12_mar2018...Nicholas Sarlis
Galinpepimut-S (WT1-targeting peptide vaccine) in high-risk multiple myeloma. Final results from a Phase 2 clinical study. Koehne G, et al. EBMT 2018 slide presentation.
• Describe the role of antibiotic use in the
development of resistance
• Review toxicity of commonly used antibiotics
• Understand the prevalence and clinical impact
of carbapenem resistant enterobacteriaceae
• State the prognosis antimicrobial resistant
Staph aureus infections
•Describe the role of antibiotic use in the development of resistance
•Review toxicity of commonly used antibiotics
•Understand the prevalence and clinical impact of carbapenem resistant enterobacteriaceae
•State the prognosis antimicrobial resistant Staph aureus infections
ASCO 2015 Melanoma Immunotherapy
Thomas Olencki, DO Division of Medical Oncology Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus, Ohio
Recent advancements in metastatic colorectal cancer treatmentKindai University
In this presentation, the presenter tries to provide an overview of the current established treatment strategies, based on their clinical outcomes as well as their mechanisms, limitations that remain to be overcome, and their future applicability for the treatment of human Colorectal Cancer.
Aflibercept in combination with fluorouracil, leucovorin, and irinotecan in t...Mary Ondinee Manalo Igot
Folfiri aflibercept poster for apcc 2015
Aflibercept in combination with fluorouracil, leucovorin, and irinotecan in the treatment of Asian patients with metastatic colorectal cancer
Primary mediastinal liposarcoma of the superior, middle, and anterior mediast...Mary Ondinee Manalo Igot
Primary mediastinal liposarcoma of the superior, middle, and anterior mediastinum
https://www.actamedicaphilippina.org/issue/1102
A case of chronic diarrhea secondary to Capillaria philippinensis in Occidental, Mindoro Philippines: a newly-diagnosed endemic area?
https://www.actamedicaphilippina.org/article/7208-a-case-of-chronic-diarrhea-secondary-to-capillaria-philippinensis-in-occidental-mindoro-possibly-a-newly-described-endemic-area
Correlation between Demographic, Socio-economic, and Cancer-Specific Factors with Quality of Life Scores among Newly-Diagnosed Cancer Patients of the Medical Oncology Clinics of the Philippine General Hospital Cancer Institute
https://www.actamedicaphilippina.org/issue/1102
Safety and efficacy of aflibercept in combination with fluorouracil, leucovor...Mary Ondinee Manalo Igot
Safety and efficacy of aflibercept in combination with fluorouracil, leucovorin and irinotecan in the treatment of Asian patients with metastatic colorectal cancer
This presentation talks about the nonconventional ways to look for cancer. It discusses next generation sequencing for multilane panels for cancer predisposition syndromes, whole genome sequencing, circulating tumor cells, circulating tumor DNA, and CancerSEEK. It also discusses the traditional cancer screening guidelines by the American Cancer Society and the USPSTF.
Electrochemotherapy for the palliative treatment of skin metastases and malig...Mary Ondinee Manalo Igot
Primary Author: Dr Claire Habito (Onco-Dermatologist)
This study observational study was done to evaluate the efficacy, safety, and clinical outcome of four-electrode electrochemotherapy device for the treatment of cutaneous metastases and malignant wounds.
Will detail on the historical chemotherapy, latest chemotherapy and a proposed chemotherapy for burst lymphoma. Will also detail on the pathophysiology of burnt lymphoma
“Cancer Anorexia Cachexia (originally Cancer Cachexia) is a multifactorial syndrome defined by:
Ongoing loss of skeletal muscle mass (with or without loss of fat mass)
Cannot be fully reversed by conventional nutritional support
Leads to progressive functional impairment”.
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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.
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
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
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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
1. Immunotherapy:
New Standard for Treating Cancers
Mary Ondinee M. Igot, MD, MSCM, FPCP, FPSMO
Medical Oncologist / Neuro – Oncologist
Asian Hospital and Medical Center
2. Outline
• Main Approaches to Cancer Immunotherapy
• The Anti-PDL1 Hype: Practice Changing Data
• Indications for giving Pembrolizumab
• Adverse events from Pembrolizumab
3. The Immune System and Cancer
http://www.oxfordimmunotec.com/international/science/technology-2/
4. The Immune System and Cancer
http://www.oxfordimmunotec.com/international/science/technology-2/
Monoclonal Antibodies
1. Rituximab (anti-CD20)
2. Trastuzumab (anti-HER2-neu)
3. Cetuximab (anti-EGFR)
4. Panitumumab (anti-EGFR)
5. Bevacizumab (anti-VEGF)
6. Ramucirumab (anti-VEGFR2)
INTERFERE WITH
GROWTH SIGNALS rather
than by direct destruction
of tumor cells
5. Immunotherapy
Goals of immunotherapy:
1. Aid in the recognition of cancer as foreign by the
immune system
2. Stimulate immune responsiveness
3. Relieve inhibition of the immune system that allows
tolerance of tumor growth
Differs from:
• Chemotherapy : targets rapidly dividing cells
• Targeted Therapies : interfere with key molecular
events in tumor cells that drive tumor growth and
invasion
6. Three Main Approaches to Cancer Immunotherapy
http://www.oxfordimmunotec.com/international/science/technology-2/
7. Three Main Approaches to Cancer Immunotherapy
http://www.oxfordimmunotec.com/international/science/technology-2/
I. Active immunization to enhance anti-
tumor reactions (cancer vaccines)
8.
9. Three Main Approaches to Cancer Immunotherapy
http://www.oxfordimmunotec.com/international/science/technology-2/
I. Active immunization to enhance anti-
tumor reactions (cancer vaccines)
II. Passively transfer activated immune cells
with anti-tumor activity (adoptive cell
transfer >> CAR T-cells)
11. • A patient with recurrent multifocal glioblastoma (brain and spine)
received multiple infusions CAR T-cells over 220 days through 2
intracranial routes (resected tumor cavity and ventricular system).
• After the treatment, regression of all the intracranial and spinal
tumors were observed and the response continued for 7.5 months
after the initiation of CAR T-cell therapy.
12. Three Main Approaches to Cancer Immunotherapy
http://www.oxfordimmunotec.com/international/science/technology-2/
I. Active immunization to enhance anti-
tumor reactions (cancer vaccines)
II. Passively transfer activated immune cells
with anti-tumor activity (adoptive
immunity)
III. Non-specific stimulation of immune
reactions
a. Stimulate effector cells
i. IL-2 (melanoma, renal cell)
13. Interleukin-2
• Soluble T-cell growth
factor
• Received FDA approvals
• 1992: metastatic renal cell
carcinoma
• 1998: metastatic
melanoma
• Both of these
malignancies had some
complete responders
• Only recommended for
high volume centers with
extensive experience in
its administraton
T-cells secrete IL-2 necessary for the
proliferation of T-cells.
14. Three Main Approaches to Cancer Immunotherapy
http://www.oxfordimmunotec.com/international/science/technology-2/
I. Active immunization to enhance anti-
tumor reactions (cancer vaccines)
II. Passively transfer activated immune cells
with anti-tumor activity (adoptive
immunity)
III. Non-specific stimulation of immune
reactions
a. Stimulate effector cells
i. IL-2 (melanoma, renal cell)
b. Inhibit regulatory factors
i. Anti-CTLA4
ii. Anti-PD1 / Anti-PDL1
15. Immune checkpoints: CTLA-4 and PD-1/PD-L1
De Vita, 10th edition
PD-1 or CTLA-4 engagement with its
ligand, lead to T-cell inactivation
Reduced cytokine
production
Reduces proliferation of T
cells
REDUCED KILLING OF CANCER CELLS
by cytotoxic T cells
== IMMUNOSTAT ==
17. • N = 676 previously treated Stage unresectable III/IV,
randomized in a 3:1:1 to receive ipilimumab + gp100 vs
gp100 vs ipilimumab alone
• Median OS with ipilimumab alone was 10.1 months (HR for
death in the comparison with gp100 alone, 0.66; P=0.003).
• No difference in overall survival was detected between the
ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04;
P=0.76).
NEJM 2010; 363; 711-723
18.
19. 2015: Era of PD-1 inhibitors (Nivolumab
and Pembrolizumab)
…. what most of us refer to as
IMMUNOTHERAPY
20.
21. NEJM 2015; 372; 2521-32.
• Randomized controlled phase 3 study
• Advanced melanoma with at least 1 prior chemotherapy,
any BRAF status
• 834 patients, 1:1:1 ratio
• Pembrolizumab every 2 weeks vs pembrolizumab every 3
weeks vs ipilimumab every 3 weeks
• Primary endpoint: Progression free survival (PFS)
• Secondary endpoints: Overall survival (OS) and adverse
events (AEs).
22. NEJM 2015; 372; 2521-32.
Pembrolizumab
every 2wks
Pembrolizumab
every 3wks
Ipilimumab
every 3 wks
6 month PFS 47.3% 46.4% 26.5%
12 month OS 74.1% 68.4% 58.2%
Response rate 33.7% 32.9% 11.9%
G3/4 AES 13.3% 10.1% 19.9%
23.
24. • Open label phase 3 study
• Previously treated advanced nonsmall cell lung CA (majority had no
EGFR mutations / ALK translocation)
• 1034 patients, 1:1:1 ratio
• Pembrolizumab 2 mg/kg vs pembrolizumab 10 mg /kg vs docetaxel
• Primary endpoint: Overall survival (OS) and progression free survival
(PFS)
• Secondary endpoints: Adverse events (AEs), determination of PDL1
receptor expression
www.thelancet.com Published online December 19, 2015
http://dx.doi.org/10.1016/S0140-6736(15)01281-7
25. www.thelancet.com Published online December 19, 2015
http://dx.doi.org/10.1016/S0140-6736(15)01281-7
Pembrolizumab
2 mg / kg
Pembrolizumab
10 mg / kg
Docetaxel 75
mg / kg
Median OS 10.4 months
(14.9 months if
PDL1 >50%)
12.7 months
(17.3 months
if PDL1 >50%)
8.7 months
(8.2 months if
PDL1 >50%)
Median PFS 3.9 months 4.0 months 4.0 months
G3/5 AES 13.0% 16.0% 35.0%
26.
27. Outside the Philippines…
• Pembrolizumab is approved for:
1. First-line treatment of advanced / metastatic NSCLC
2. Recurrent / Metastatic Head and Neck SCCA
3. MSI-High Colorectal Cancer
4. Relapsed / Refractory Classical Hodgkin’s Lymphoma after
Failure of Brentuximab
5. Second-line treatment for Advanced Urothelial Carcinoma
28.
29.
30.
31.
32. Published online at NEJM.org, February 17, 2017.
• Open label phase 3 study
• Previously treated advanced / metastatic urothelial carcinoma
• At least 10% PD-L1 positive
• 542 patients, 1:1 ratio
• Pembrolizumab 200 mg every 3 weeks vs investigator’s choice of
chemotherapy
• Primary endpoint: Overall survival (OS) and progression free survival
(PFS)
• Secondary endpoints: Adverse events (AEs)
33. Published online at NEJM.org, February 17, 2017.
Pembrolizumab 200 mg
every 3wks
Investigator’s Choice of
Chemotherapy
Median PFS (p=0.42) 2.1 months 3.3 months
Median OS (p=0.005) 10.3 months 7.4 months
G3/5 AES 15.0% 49.4%
35. Published online November 2016.
• HYPERPROGRESSIVE DISEASE (HPD): RECIST progression at the first
evaluation and as a >/= 2 fold increase in tumor growth rate
• Retrospective study of phase I trials
• 9% had HPD
• Associated with older age and shorter survival
• In another study: The amplification of MDM2 is also associated with
hyperprogression after the initiation of immunotherapy.The pace of
progression was increased anywhere from 5-40 fold.
36. In a nutshell
• Immunotherapy can be in the form of vaccines, CAR T- cells, IL-2
and checkpoint inhibitors.
• For pembrolizumab: when PD-1 integrates with PD-L1,an
IMMUNOSTAT is produced that leads to T-cell inactivation and
reduced tumor cell killing.
• Blocking this pathway will free the cytotoxic T- lymphocytes and
facilitate tumor cell killing.
• PD-1 inhibitors are effective and have a favorable side effect
profile.
• Further studies are ongoing that will guide us on appropriate
patient selection.
Next is through transfer of T cells, or what we know now as CART cell therapy.
Just 2 months ago, a case report was published that with the help of CAR T-cells, multifocal glioblastoma regressed in size.
.
Wherein a T cell can just be beside a cancer cell and do nothing, instead of acting against it.
The most popular of the CTLA4 inhibitors is IPILIMUMAB.
This is the study that got ipilimumab its FDA approval for metastatic melanoma in 2010.
It randomized 676 patients into ipilimumab plus a vaccine vs the vaccine alone, vs ipilimumab alone.
Median overall survival with ipilimumab alone was 10.1 months and it showed no difference with the combination arm. Prior to this study, after chemotherapy patients would onl live for less than 3 months so this was a big development for the field of melanoma.
In 2013, several phase 1 and 2 trials came out with very promising results. PD1/PDL1 antagonists were labelled as the drug of the year because long term tumor control was now achievable.
In 2015, we entered the era of PD-1 inhibitors, nivolumab and pembrolizumab as their PHASE III data came out. These are what we commonly refer to now as IMMUNOTHERAPY. But actually, in the previous decades, we have already been giving immunotherapy, but with different targets.
In the interest of time, I will not be discussing trials on Nivolumab as it is not available in the Phils.
Prior to making this presentation, I asked the MSD product lead what the approved indications were in the Philippines and this is what I got for an answer. Presently, it is only approved for metatstatic melanoma and nonsmall cell lung cancer who have progressed on chemotherapy.
This study investigated pembrolizumab vs ipilimumab in patients with advanced melanoma who had received at least 1 prior chemotherapy. The primary endpoint was progression free survival and secondary endpoints were overall survival and adverse events
Pembrolizumab was superior to ipilimumab in terms of progression free and overall survival. Response rate more than doubled and severe adverse events were less frequently reported.
Because of that pivotal paper, pembrolizumab was incoprporated in our guidelines and considered as standard of care.
The next study investigated pembrolizumab vesus docetaxel in previously treated, PDL1 positive advanced nonsmall cell lung cancer.
It was an open label phase 3 study, where they also determined the PDL1 status of the tumors
Summarized are the results:
For unselected patients, pembrolizumab was better than chemotherapy in terms of overall survival and progression free survival. It also had a better side effect profile.
When they examined the degree of PDL1 expression, they noted that those patients with a PDL1 expression of more than 50% had the most benefit in terms of survival. Patients were living up to 17 months on pembrolizumab vs 8 months on chemotherapy.
Shown here is the incorporation of immunotherapy in lung cancer second line.
To summarize again, here it is only approved for metastatic melanoma and for lung cancer second line.
Outside the Philippines, Pembro is approved for the following indications
Pembro is already approved as first line for lung cancer provided that it does not harbor any mutations and translocations and its PDL1 expression is more than 50%. It received category 1 recommendation.
It is also approved for recurrent/netastatic/unresectable head and neck squamous cell cancer on or after chemotherapy.
In the pivotal papers that were published that had pembrolizumab approved for its specific indications, there was no report of heart failure. But Dr De los Reyes will likely discuss that