This document summarizes information about immunotherapy for non-small cell lung cancer (NSCLC). It provides data on key clinical trials that evaluated immunotherapy drugs like nivolumab and pembrolizumab in previously treated NSCLC. It shows the efficacy results including overall survival benefits from these trials compared to chemotherapy. Long-term survival outcomes are also presented from pooled analyses of nivolumab trials with over 3 years of follow-up data.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
Optimizing Therapeutic Strategies in Castration-Resistant Prostate Canceri3 Health
This activity will discuss emerging efficacy and safety data on novel therapies for nmCRPC and mCRPC, strategies to manage adverse events, and the role of imaging studies and PSA testing in evaluating treatment response.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Aim of this ppt presentation:
To understand the standard of care for both GBM and anaplastic glioma.
To know what is the new advances and modifications to the standard of care?
Contents:
Introduction: 2 slides.
GBM:
Epidemiology: 1 slide.
Molecular biology & New trends: 5 slides
EORTC/NCIC trial: 10 slides.
MGMT: 1 slide.
Evidence-based medicine: 6 slides.
Avastin in GBM: 2 slides.
Novocure (TTF): 2 slides.
Gliadel (BCNU) wafers: 1 slide.
Anaplastic astrocytoma: 7 slides
Take home message.
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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
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
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
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
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!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
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
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Tipo Mundo Estados Unidos Colombia
Incidencia Mortalidad Incidencia Mortalidad Incidencia Mortalidad
Todo 201 100.7 362.2 86.3 182.3 84.7
Mama 47.8 13.6 90.3 12.4 48.3 13.1
Próstata 30.7 7.7 72.0 8.2 49.8 11.9
Pulmón 22.4(3) 18.0(1) 33.1(3) 18.9(1) 10.5(6) 9.2(4)
Colo-recto 19.5 9.0 25.6 8.0 16.9 8.2
Cérvix 13.3 7.3 6.2 2.1 14.9 7.4
Estómago 11.1 7.7 4,2 1.7 12.8 9.9
Hígado 9.5 8.7 6.9 4.7 3.5 3.4
Endometrio 8.7 1.8 21.4 3.1 8.1 1.7
Ovario 6.6 4.2 8.1 4.0 7.5 4.5
Esófago 6.3 5.6 2.4 2.8 1.3 1.2
Tiroides 6.6 0.4 11.8 0.3 9.1 0.7
Páncreas 4.9 4.5 8.2 6.6 4.1 4.0
Leucemia 5.4 3.3 11.1 3.2 6.2 4.1
Incidencia y mortalidad por cáncer en el Mundo, Estados
Unidos y Colombia
GLOBOCAN - 2020
/100.000 habitantes-año
4.
5.
6. Kris MG, et al. ASCO 2011. CRA7506. Johnson BE, et al. IASLC WCLC 2011. Abstract O16.01
Lung Cancer Molecular Consortium Analysis in
Lung Adenocarcinomas
No Mutation
Detected KRAS
22%
EGFR
17%
EML4-AKL
7%
BRAF 2%
PIK3CA 2%
HER2
MET AMP
MEK1
NRAS
AKT1
7. Metastatic NSCLC fit
for cancer therapy
Actionable
mutations?
EGFR ALK ROS1
Afatinib
Osimertinib
etc
Alectinib
Crizotinib
Crizotinib
Yes
PD-L1
≥50%
PD-L1
≤50%
Not an IO
candidate
No
9. Study Treatment Arms
Median OS
(mos) 1-Year Survival
TAX 317[a]
Docetaxel (N = 103) 7.0 37.0%
Best supportive care (N = 100) 4.6 12.0%
Hanna et al. 2004[b]
Pemetrexed (N = 283) 8.3 29.7%
Docetaxel (N = 288) 7.9 29.7%
INTEREST[c]
Gefitinib (N = 723) 7.6 32.0%
Docetaxel (N = 710) 8.0 34.0%
TITAN[d]
Erlotinib (N = 203) 5.3 26.0%
Chemotherapy (N = 221: 116
docetaxel, 105 pemetrexed)
5.5 24.0%
Second-Line Therapy: Options & Outcomes
a. Shepherd FA, et al. J Clin Oncol. 2000;18:2095-2103.
b. Hanna N, et al. J Clin Oncol. 2004;22:1589-1597.
c. Kim ES, et al. Lancet. 2008;372:1809-1818.
d. Ciuleanu T, et al. Lancet Oncol. 2012;13:300-308.
10. Second-Line Therapy: Options & Outcomes
a. Shepherd FA, et al. J Clin Oncol. 2000;18:2095-2103.
b. Hanna N, et al. J Clin Oncol. 2004;22:1589-1597.
13. Efficacy of Nivolumab Monotherapy in Pts With Previously
Treated Advanced NSCLC
Gettinger SN, et al. J Clin Oncol. 2015;33:2004-2012.
Nonsquamous
Squamous
0 6 12 18 24 30 36 42
Mos Since Treatment Initiation
Time to and duration of response until
discontinuation of therapy
Ongoing response
Time to response
Duration of response after discontinuation of
therapy
1 yr: 42%
2 yrs: 24%
3 yrs: 18%
48 54 60 66
24 30 36 42
0 6 12 18
Mos Since Treatment Initiation
100
80
60
40
20
0
OS
(%)
Died/Treated
99/129
Median, Mos
9.9
95% CI
7.8-12.4
1 yr: 56%
2 yrs: 42%
3 yrs: 27%
48 54 60 66
24 30 36 42
0 6 12 18
Mos Since Treatment Initiation
100
80
60
40
20
0
OS
(%)
Died/
Treated
26/33
23/37
50/59
Median,
Mos
9.2
14.9
9.2
95% CI
5.3-11.1
7.3-30.3
5.2-12.4
Squamous
Nonsquamous
120 140 160
80 100
0 20 40 60
Wks Since Treatment Initiation
120
80
40
0
-40
-100
Change
in
Target
Lesion
From
Baseline
(%)
mg/kg
1
3
10
100
60
20
-20
-80
-60
14. Survival
Time
Modified from Ribas A, et al. Clin Cancer Res. 2012;18:336-341.
Survival Pattern with Chemotherapy and Immune checkpoint
blockade
Immune checkpoint
Chemotherapy
17. Inclusion
Stage IIIB or IV squamous-cell NSCLC
who had disease recurrence after one
prior platinum-containing regimen
18 years of age or older
ECOG performance-status score of 0 or 1
Tumor-tissue specimen for biomarker
analyses.
Treated, stable brain metastases were eligible.
Prior maintenance therapy, including an
epidermal growth factor receptor tyrosine
kinase inhibitor, was allowed.
Exclusion
Key exclusion criteria were
autoimmune disease,
Symptomatic interstitial lung
disease, Systemic
immunosuppression,
Prior therapy with T-cell
costimulation or checkpoint-
targeted agents, or
Prior docetaxel therapy.
Patients who had received more
than one prior systemic therapy
for metastatic disease were
excluded
R
(1:1)
272 pts
Nivolumab
Docetaxel
End-point: OS
CheckMate 017
Brahmer J, NEJM, 2015
19. Inclusion
Stage IIIB or IV or recurrent
nonsquamous NSCLC disease recurrence
or progression during or after one prior
platinum-based doublet.
Patients with known EGFR mutation
or ALK translocation were allowed to
have received or be receiving an
additional line of tyrosine kinase
inhibitor therapy, and a continuation of
or switch to maintenance therapy with
pemetrexed, bevacizumab, or erlotinib
was allowed in all patients.
18 years of age or older
ECOG performance-status score of 0 or 1
Exclusion
Exclusion criteria were
autoimmune disease,
symptomatic interstitial
lung disease, systemic
immunosuppression, prior
treatment with immune-
stimulatory antitumor
agents including
checkpoint-targeted
agents, and prior use of
docetaxel
R
(1:1)
292 pts
Nivolumab
Docetaxel
End-point: OS
CheckMate 057
Borghaei H, NEJM, 2015
22. Pembrolizumab in NSCLC (KEYNOTE-001 Cohort): OS by PD-
L1 Expression
Pts at Risk, n
119 92 56 22 5 4 3 0
161 119 58 15 6 4 0 0
76 55 33 8 0 0 0 0
100
80
60
40
20
0
0 4 8 12 16 20 24 28
OS
(%)
Mos
PS 1-49%
PS < 1%
PS ≥ 50%
PS
Median OS,
Mos (95% CI)
≥ 50% NR (13.7-NR)
1-49% 8.8 (6.8-12.4)
< 1% 8.8 (5.5-12.0)
Garon EB, et al. N Engl J Med. 2015;372:2018-2028. Garon EB, et al. AACR 2015. Abstract CT04.
23. Inclusion
Advanced NSCLC
Confirmed PD after ≥1 line of
chemotherapy
No active brain metastases
ECOG PS 0-1
PD-LS TPS ≥1%
No serious autoimmune disease
No ILD or pneumonitis requiring
systemic steroids
R
(1:1:1)
1034 pts
Pembro 10/kg
Docetaxel
End-point: OS and PFS
KEYNOTE-010
Herbst RS, The Lancet, 2016
Pembro 2/kg
27. Inclusion
Squamous or non-squamous non-
small-cell lung cancer.
Patients had received one to two
previous cytotoxic chemotherapy
regimens (one or more platinum
based combination therapies) for
stage IIIB or IV non-small-cell lung
cancer.
EGFR/ALK+ had to have received TKIs
Treated asymptomatic supratentorial brain
metastasis were allowed
18 years or older,
Measurable disease per RECIST
ECOG PS 0/1
Exclusion
Patients with a history of
autoimmune disease and
those who had received
previous treatments with
docetaxel, CD137 agonists,
anti-CTLA4, or therapies
targeting the PD-L1 and PD-1
pathway were excluded.
R
(1:1)
850 pts
Atezolizumab
Docetaxel
End-point: Coprimary endpoints were overall survival in
the intention-to-treat (ITT) and PD-L1-expression
population TC1/2/3 or IC1/2/3 (≥1% PD-L1 on tumour
cells or tumour-infiltrating immune cells)
OAK
Rittmeyer A, The Lancet, 2017
30. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
Table 1. Studies included in the pooled analyses
Study Histology Phase Treatment
Patients,
N
Dose
Current follow-up
median (range),
monthsb
CheckMate 0034,6
NCT00730639
Squamous/
non-squamous
1 Nivolumab 129
1, 3, or 10 mg/kg
Q2W
9.2 (0.5−106.9)c
CheckMate 0637
NCT01721759
Squamous 2 Nivolumab 117 3 mg/kg Q2W 8.0 (0−62.2)c
CheckMate 0178
NCT01642004
Squamous
3
(Randomized)
Nivolumab
Docetaxel
135
137
3 mg/kg Q2Wa
75 mg/m2 Q3Wa
9.2 (0.3−62.1)d
6.0 (0.4−60.0)d
CheckMate 0579
NCT01673867
Non-squamous
3
(Randomized)
Nivolumab
Docetaxel
292
290
3 mg/kg Q2Wa
75 mg/m2 Q3Wa
12.2 (0.2−62.7)d
9.3 (0−61.4)d
30
aAfter the readout of the primary endpoint of CheckMate 017 and 057, nivolumab-treated patients were allowed to transition to nivolumab 480 mg Q4W. Eligible patients in docetaxel arms no longer
deriving benefit could cross over to nivolumab 3 mg/kg Q2W or 480 mg Q4W. In CheckMate 017 and 057, 7 and 15 patients, respectively, received nivolumab 480 mg Q4W; bDatabase lock was
May 11, 2018 for CheckMate 003, and May 18, 2018 for CheckMate 063, 017, and 057; cMedian follow-up time is based on all patients treated with nivolumab; dMedian follow-up time is based on all
patients randomized.
Q2W, every 2 weeks; Q3W, every 3 weeks; Q4W, every 4 weeks.
31. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
Figure 1. OS in all nivolumab-treated patients from
CheckMate 003/ 063/ 017/ 057a
31
Nivolumab
(N = 664)
Median OS
(95% CI), mo
10.3
(9.2, 11.9)
6 18 24 36 42 54 60 72 78 90 96 102
Months
12 30 48 66 84 108
62
664 430 299 164 104 92 28 16 13 2 1 0
214 123 82 16 4 1
46%
26%
17% 14%
100
0
40
60
80
20
0
OS
(%)
No. at risk
Nivolumab
aMedian duration of response in all patients with a CR/PR (n = 122) was 19.1 months (95% CI, 14.7−29.9).
CI, confidence interval.
32. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
Figure 2. OS with nivolumab vs docetaxel in CheckMate 017/ 057a
32
Nivolumab
(n = 427)
Docetaxel
(n = 427)
Median OS
(95% CI), mo
11.1
(9.2, 13.1)
8.1
(7.2, 9.2)
427 264 145 84 45 34 19
57 26 11 1 0
100
0
40
60
80
20
34%
14%
8%
5%
14%
17%
48%
27%
427 280 205 150 84 70 55
113 64 37 9 0
Nivolumab
Docetaxel
No. at risk
Nivolumab
Docetaxel
Months
0 6 18 24 30 42 48 60
12 36 54 66
OS
(%)
aIn the nivolumab and docetaxel arms, 4.0% (17/427) and 10.1% (43/427) of patients, respectively, received subsequent immunotherapy (includes 23 patients who crossed over from the
docetaxel arm to the nivolumab arm); 5 of 19 patients (26.3%) originally randomized to docetaxel and still alive at database lock received immunotherapy as subsequent therapy.
33. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
33
163 73
105 52 38 27 15
18 12 9 5 0
PD-L1 expression < 1%
100
0
40
60
80
20
Months
153 50
95 31 20 13 9
10 6 3 1 0
OS
(%)
0 12
6 18 24 30 42
36 48 54 60 66
34%
13%
7%
4%
9%
12%
45%
24%
Nivolumab
Docetaxel
No. at risk
Nivolumab
Docetaxel
PD-L1 expression ≥ 1%
Months
Nivolumab
Docetaxel
OS
(%)
100
0
40
60
80
20
0 12
6 18 24 30 42
36 48 54 60 66
34%
15%
10%
21%
4%
20%
54%
32%
185 99
123 76 58 42 36
38 33 20 4 0
179 61
112 36 27 23 10
17 8 5 0 0
No. at risk
Nivolumab
Docetaxel
Figure 3. OS with nivolumab vs docetaxel by tumor
PD-L1 expression in CheckMate 017/ 057a
Nivolumab
(n = 185)
Docetaxel
(n = 179)
Median OS
(95% CI), mo
13.4
(10.0, 17.7)
8.5
(7.0, 9.3)
Nivolumab
(n = 163)
Docetaxel
(n = 153)
Median OS
(95% CI), mo
9.7
(7.6 13.3)
7.8
(6.7, 10.5)
aIn all randomized patients from CheckMate 017 and 057 with evaluable PD-L1 expression.
34. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
34
18%
SD
CR/PR
PD
62%
38%
26%
35%
7%
22%
12%
8%
Months from 6-month landmark analysis
SD
CR/PR
PD
58%
81%
63% 61%
35%
24%
40%
13%
8%
70 57
65 52 44 42 37
39 24 7 0 0
66 38
53 29 23 18 13
15 10 2 0 0
144 55
87 32 17 10 5
10 3 0 0 0
CR/PR
(n = 34)
SD
(n = 102)
PD
(n = 128)
Median OS
(95% CI), mo
17.1
(11.1, 28.7)
8.0
(6.6, 10.4)
4.8
(3.4, 5.9)
HR vs PD (95% CI)
0.43
(0.29, 0.65)
0.80
(0.61, 1.04)
–
Figure 4. Landmark analysis of OS by response category status at
6 months in CheckMate 017/ 057a
CR/PR
(n = 70)
SD
(n = 66)
PD
(n = 144)
Median OS
(95% CI), mo
NR
(25.6, NR)
16.1
(10.2, 23.5)
9.1
(6.2, 11.4)
HR vs PD (95% CI)
0.18
(0.12, 0.27)
0.52
(0.37, 0.71)
–
Nivolumab Docetaxel
aIn all randomized patients from CheckMate 017 and 057 studies alive at the 6-month landmark; 65.6% and 61.8% in the nivolumab and docetaxel treatment arms, respectively, were included.
NR, not reached
Months from 6-month landmark analysis
34 21
30 15 13 10 7
9 4 0 0 0
102 35
63 24 17 11 4
7 2 0 0 0
128 28
52 18 15 13 8
10 5 1 0 0
OS
(%)
100
0
40
60
80
20
0 12
6 18 24 30 42
36 48 54 60 66
OS
(%)
0
40
60
80
20
0 12
6 18 24 30 42
36 48 54 60 66
No. at risk
CR/PR
SD
PD
No. at risk
CR/PR
SD
PD
100
58%
19%
4%
12%
2%
5%
35. LT OS & Impact of Early Response/Disease Control With Nivolumab in 2L+ NSCLC
Figure 5. OS from time of response with nivolumab vs docetaxel
in CheckMate 017/ 057a
35
Nivolumab
(n = 83)
Docetaxel
(n = 48)
Median OS post response
(95% CI), mo
NR
(26.4, NR)
16.5
(11.8, 22.1)
Median DOR
(95% CI), mo
23.8
(11.4, 36.1)
5.6
(4.4, 7.0)
OS
post
response
(%)
Months
65%
33%
23%
12%
54%
57%
87%
65%
Nivolumab
Docetaxel
83 78 71 62 47 46 36
53 40 17 2
48 45 31 22 15 11 6
16 10 3 0
0
0
No. at risk
Nivolumab
Docetaxel
100
0 6 18 24 30 42 48 60
0
40
60
80
20
12 36 54 66
aOS was calculated from the time of response (CR/PR) for each responder.
46. KEYNOTE-024: First-line Pembrolizumab for
Advanced NSCLC
Primary endpoint: PFS by BICR
Secondary endpoints: ORR, OS, and safety
Patients with untreated stage IV
NSCLC; ECOG PS 0/1;
no actionable EGFR/ALK mutations;
PD-L1 TPS ≥ 50%*;
no untreated CNS mets or active
autoimmune disease requiring tx
(N = 305)
Pembrolizumab 200 mg IV Q3W
for up to 35 cycles
(n = 154)
Plt-doublet CT
(histology based) for 4-6 cycles
(n = 151)
Until PD or
unacceptable toxicity
Stratified by ECOG PS (0 vs 1), histology
(squamous vs nonsquamous), and enrollment
region
Until PD
(crossover to
pembrolizumab allowed)
*≥ 50% tumor cell staining using 22C3 companion diagnostic IHC assay.
Slide credit: clinicaloptions.com
Open-label, randomized phase III study
Reck. NEJM. 2016;375:1823. Reck. J Clin Oncol. 2019;37:537.
49. Patients with untreated
stage IV NSCLC
ECOG PS 0/1;
no actionable EGFR/ALK
mutations
PD-L1 TPS ≥ 50%
R
(1:1)
568 pts
Ipilimumab +
Pembrolizumab
Pembrolizumab
End-point: OS and PFS
KEYNOTE-598
Boyer M, JCO, 2021
52. KEYNOTE-407: Carboplatin + Paclitaxel/nab-Paclitaxel ±
Pembrolizumab in NSCLC
Randomized, double-blind phase III trial
Primary endpoint: PFS by RECIST v1.1 (BICR), OS
Secondary endpoints: ORR and DoR by RECIST v1.1 (BICR), safety
Paz-Ares. NEJM. 2018;379:2040. Slide credit: clinicaloptions.com
Pembrolizumab + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycles x 4
(n = 278)
Patients with untreated stage IV
squamous NSCLC, ECOG PS 0/1,
available tumor biopsy for PD-L1
assessment, no brain mets, and
no pneumonitis requiring
systemic steroids
(N = 559)
Stratified by PD-L1 TPS (< 1% vs ≥ 1%), taxane (paclitaxel
vs nab-paclitaxel), region (east Asia vs other)
Carboplatin AUC 6 Q3W, nab-paclitaxel 100 mg/m2 QW, paclitaxel 200 mg/m2 Q3W, pembrolizumab 200 mg Q3W.
*Upon confirmation of PD and safety criteria by BICR, optional crossover could occur during combination or monotherapy.
Placebo + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycles x 4
(n = 281)
Pembrolizumab
up to 31 cycles
Placebo
up to 31 cycles
Pembrolizumab
up to 35 cycles
Crossover
allowed*
PD
53. KEYNOTE-407: OS (ITT)
Paz-Ares. NEJM. 2018;379:2040. Slide credit: clinicaloptions.com
Mos
Patients
at Risk, n
Pembro + CT
CT
OS
(%) Median OS,
Mos (95% CI)
15.9 (13.2-NE)
11.3 (9.5-14.8)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Pembro + CT
CT
HR: 0.64
(95% CI: 0.49-0.85; P < .001 )
278
281
256
246
188
175
124
93
62
45
17
16
2
4
0
0
54. KEYNOTE-407: OS by Subgroup
Paz-Ares. NEJM. 2018;379:2040. Slide credit: clinicaloptions.com
Subgroup
Overall
Age
Sex
ECOG PS
Region of enrollment
PD-L1 tumor proportion score
Choice of taxane
0.64 (0.49-0.85)
0.52 (0.34-0.80)
0.74 (0.51-1.07)
0.69 (0.51-0.94)
0.42 (0.22-0.81)
0.54 (0.29-0.98)
0.66 (0.48-0.90)
0.44 (0.22-0.89)
0.69 (0.51-0.93)
0.61 (0.38-0.98)
0.65 (0.45-0.92)
0.57 (0.36-0.90)
0.64 (0.37-1.10)
0.67 (0.48-0.93)
0.59 (0.36-0.98)
HR (95% CI)
CT Better
Pembro + CT Better
0.1 0.5 1.0
< 65 yrs
≥ 65 yrs
Male
Female
0
1
East Asia
Rest of world
< 1%
≥ 1%
1% to 49%
≥ 50%
Paclitaxel
nab-Paclitaxel
Deaths/Patients, n/N
205/559
88/254
117/305
167/455
38/104
48/163
157/396
34/106
171/453
73/194
129/353
76/207
53/146
140/336
65/223
64. IMpower150: Addition of Atezolizumab to Carbo/Pac +
Bevacizumab in Advanced NSCLC
Randomized phase III study
Patients with stage IV or
recurrent, chemotherapy-
naive nonsquamous NSCLC
(PD on or intolerance to
targeted agents allowed);
available tumor tissue
(N = 1202)
Carboplatin/Paclitaxel Q3W +
Bevacizumab 15 mg/kg IV Q3W
(n = 336; control arm)
Atezolizumab 1200 mg IV Q3W +
Carboplatin/Paclitaxel Q3W +
Bevacizumab 15 mg/kg IV Q3W
(n = 356)
Atezolizumab
until PD or loss of
benefit and/or
bevacizumab
until PD
Bevacizumab
Atezolizumab +
Bevacizumab
Stratified by sex, PD-L1 expression, liver mets
4-6 cycles
Reck. ESMO I-O Congress 2017. Abstr LBA1_PR. Kowanetz. AACR 2018. Abstr CT076. Socinski. NEJM. 2018;378:2288. Slide credit: clinicaloptions.com
Maintenance therapy
(no crossover allowed)
Primary endpoints: PFS, OS
Secondary endpoints: PFS (IRF), ORR, OS at Yrs 1 and 2, QoL, safety, PK
66. IMpower150: Landmark OS in ITT Population (Including
Patients With EGFR and ALK Aberrations)
Clinically meaningful OS benefit with atezolizumab + bevacizumab + chemotherapy vs bevacizumab
+ chemotherapy was observed in all patients
Socinski. ASCO 2018. Abstr 9002. Slide credit: clinicaloptions.com
HR: 0.76
(95% CI: 0.63-0.93)
Median follow-up: ~ 20 mos
100
90
80
70
60
50
40
30
20
10
0
OS
(%)
Mos
34
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
Atezolizumab +
Carbo/Pac + Bev
(n = 400)
Carbo/Pac
+ Bev
(n = 400)
Median OS, mos
(95% CI)
19.8
(17.4-24.2)
14.9
(13.4-17.1)
12-mo OS, % 68 61
18-mo OS, % 54 42
24-mo OS, % 45 36
67. IMpower150: OS by Subgroup
Socinski. ASCO 2018. Abstr 9002. Slide credit: clinicaloptions.com
Favors
Atezolizumab + Carbo/Pac + Bev
Favors
Carbo/Pac + Bev
*For prevalence, ITT WT (n = 696) used for PD-L1,
liver metastases groups; ITT (n = 800) for rest.
Median OS, Mos
25.2
20.3
17.1
13.2
19.8
19.8
NE
19.2
15.0
16.4
14.1
9.1
16.7
14.9
17.5
14.7
Subgroup
PD-L1 high (TC3 or IC3) WT
PD-L1 low (TC1/2 or IC1/2) WT
PD-L1 negative (TC0 and IC0) WT
Liver metastases WT
No liver metastases WT
ITT (including EGFR/ALK+)
EGFR/ALK+ only
ITT WT
n (%)*
136 (20)
226 (32)
339 (49)
94 (14)
602 (86)
800 (100)
104 (13)
696 (87)
0.2 1.0 2.0
HR
HR
0.70
0.80
0.82
0.54
0.83
0.76
0.54
0.78
ABCP BCP
68. Inclusion
Squamous or nonsquamous stage
IV or recurrent NSCLC
PD-L1≥1%
ECOG 0/1
None of the patients had received
previous systemic anticancer
therapy for advanced or
metastatic disease.
Exclusion
EGFR mutations or
known ALK translocations
sensitive to targeted therapy,
Autoimmune disease,
Untreated or symptomatic central
nervous system metastases.
R
(1:1)
1166 pts
Nivolumab +
Ipilimumab
Platinum doublet
chemotherapy
End-point: OS
CheckMate 227 (PD-L1 ≥1% cohort)
Hellman MD, NEJM, 2019
74. Conclusiones
74
mNSCLC – candidato a tratamiento
Mutación accionable Terapia blanco-dirigida
PD-L1 ≥ 50% Considerar pembrolizumab
PD-L1 <50% - Alta carga tumoral Quimio + IO o IO+IO
Sí
Sí
Sí
Sí
No
No
mEGFR
Lux-Lung 3/6
FLAURA
RELAY
ALK+
ALEX
PROFILE1014
KEYNOTE-24
No-escamosos
IMpower150
KEYNOTE-189
Escamosos
KEYNOTE-407
Arte
75. Supervivencia a los 12 meses
50%
73%
79%
90%
Quimioterapia
Inmunoterapia
+/- quimioterapia
ROS1
Crizotinib
mEGFR/ALK
Terapia Dirigida
76. mNSCLC fit for
therapy
Mutaciones
accionables
PD-L1 ≥50% Otros
Escamo.
IO-IO
CT + IO
Pembro + CT6
Nivo + Ipi + CT4
Nivo + Ipi5
No
Ecamo.
IO-IO
CT + IO
Pembro + CT2
Atezo (+Bev) + CT3
Nivo + Ipi + CT4
Nivo + Ipi5
Pembro1
Terapia dirigida
Atezo (+Bev) + CT3
cuando la terapia
dirigida ya no
funciona
1. KN-024
2. KN-189
3. IMpower150
4. CM-9LA
5. CM-227
6. KN-407
IO’s crowded space in mNSCLC 1L
20% 20%
20%
60%
40%
Spanglish Oncology