Opportunities for Immune Therapy and Preventionbkling
Dr. Margaret Gatti-Mays of the National Cancer Institute, a Staff Clinician of Laboratory of Tumor Immunology and Biology and the Co-Director of the Clinical Trial Group, explores the future of immunotherapy in breast cancer treatment.
Opportunities for Immune Therapy and Preventionbkling
Dr. Margaret Gatti-Mays of the National Cancer Institute, a Staff Clinician of Laboratory of Tumor Immunology and Biology and the Co-Director of the Clinical Trial Group, explores the future of immunotherapy in breast cancer treatment.
Chair and Presenter, Jonathan D. Spicer, MD, PhD, FRCSC, Sara Najmeh, MD, and Paula A. Ugalde Figueroa, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Neoadjuvant, Adjuvant, or Both: How to Solve the Puzzle of Perioperative Immunotherapy, Individualize Treatment Plans, and Improve Cure Rates in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3K8tKH9. CME/MOC credit will be available until June 5, 2024.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
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.
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
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.
Chair and Presenter, Jonathan D. Spicer, MD, PhD, FRCSC, Sara Najmeh, MD, and Paula A. Ugalde Figueroa, MD, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Neoadjuvant, Adjuvant, or Both: How to Solve the Puzzle of Perioperative Immunotherapy, Individualize Treatment Plans, and Improve Cure Rates in Resectable NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3K8tKH9. CME/MOC credit will be available until June 5, 2024.
Strategies for Managing Recurrent Ovarian Cancerbkling
When ovarian cancer returns, it's not uncommon to experience a range of emotions and feel overwhelmed. But it's important to remember that recurrent ovarian cancer can often be successfully treated. Dr. Shannon N. Westin, gynecologic oncologist and clinical investigator at MD Anderson Cancer Center, goes over the latest treatment options for recurrent disease.
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.
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
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.
Report Back from San Antonio Breast Cancer Symposium: Spotlight on MBCbkling
Dr. Virginia Kaklamani, Leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, will share her biggest takeaways from the latest research presented at the San Antonio Breast Cancer Symposium (SABCS) 2019 with a focus on metastatic breast cancer.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
Dr. Manuel Hidalgo - Simposio Internacional ' Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
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.
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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.
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
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
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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
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.
How to Give Better Lectures: Some Tips for Doctors
Role of Apalutamide in management of M0 CRPC
1. Management of Non Metastatic
CRPC
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
JNJ Meeting
Cairo Semiramis Intercontinental Hotel
06/09/2018
2. Member of Advisory Board, Consultant, and Speaker for:
• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer, Mundipharma, MSD, Ely Lilly, Sanofi-
Genzyme.
Speaker Disclosures:
3. Prostate Cancer:
Positioning of Available Therapies:
Locoregional
Disease
Biochemical
Failure
Metastatic
“Sensitive”
Metastatic
“Refractory”
Death
TIME
TumorBurden
Androgen Deprivation Therapy
1st Generation
Anti-Androgen
2nd Generation
Anti-Androgen
Biosynthesis
Cytotoxic
Anti-microtubule
4. Prostate Cancer: Emerging Challenges
• Screening Programs:
M1 or PSA > 100 ng/dl at presentation: 7.9% 2.6%
• ADT is increasingly used earlier plus other
loco-regional procedures CRPC
• Increasing number of nmCRPC.
Schroder et al. N Engl J Med 2012; 366(11): 981–990.
Taille A. journal de l’Association francaise d’urologie et de la Societe francaise d’urologie 2009; 19(5): 313–320.
Tombal B. Annals of Oncology 23 (Supplement 10): x251–x258, 2012
6. M0 CRPC: New Chapter of Story
M0CRPC M1CRPC
Longer
• Symptomatic QoL
• Survival.
Kirby et al. Int J Clin Pract 2011; 65(11): 1180–1192.
7. Definition of M0CRPC
• A rising PSA that is 2 ng/mL higher than the
nadir with a rise of at least 25% over nadir.
• The rise must be confirmed by a second PSA at
least 3 weeks later.
• The patient must have castration levels of
testosterone (<50 ng/mL).
• No radiographic evidence of metastatic
disease.
Scher et al. Recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008;26:1148-59.
9. M0 CRPC: Imaging Schedule:
• RADAR GROUP:
– Start on diagnosis of CRPC (or PSA > 2ng.ml)
– 2nd when 5 ng/ml
– Repeat with every doubling of PSA.
• Procedures: BS, CT, MRI.
• Other newer modalities (PSMA)??
David M. Albala. Rev Urol. 2017;19(3):200–202
10. Newer Imaging Modalities in Prostate
Cancer
Tracer Target Context/Indication Regulatory Status
C-11
Choline[1] Lipid
synthesis
Suspected prostate cancer
recurrence and
noninformative bone
scintigraphy, CT, or MRI
FDA approved (2012)
Limited availability (in US)
Fluciclovine[
2]
Amino
acid
transpor
t
Suspected prostate cancer
recurrence based on
elevated PSA following
prior Tx
FDA approved (2016)
Commercially available;
variable reimbursement
Ga68-
PSMA-11[3] PSMA Multiple; all investigational
Approved in non-US countries
Available, including trials
[F-18]-
DCFPyL[4] PSMA Multiple; all investigational
Approved in non-US countries
Available, including trials
1. Choline C 11 PI. 2012. 2. Fluciclovine F-12 PI. 2016. 3. ClinicalTrials.gov. 4. ClinicalTrials.gov. NCT03501940.
11. M0 CRPC in 2018:
APALUTAMIDE ENZALUTAMIDE
Competitive Inhibition
of AR Signaling
DNA Binding Domain
Translocation to
Nuclear Membrane
Androgen Binding
DomainLess CNS Permeation
Chandler & De Bono. Nature Reviews June 2018.
volume 15
12. Eligibility
• nmCRPC
- Negative 99mTc bonescan
- Negative CT of pelvis,
abdomen, chest, andbrain
- Pelvic nodes < 2 cmbelow
iliac bifurcation (N1)
allowed
• PSADT ≤ 10 months
On-Study Requirement
• ContinuousADT
Stratifications
• PSADT > 6 mo or ≤ 6mo
• Bone-sparing agents,y/n
• N0 or N1
Second Rx
at MD’s
discretion
including
open-label
AA+P
Apalutamide
(APA)
240 mg QD
+ ADT
(n = 806)
Placebo (PBO)
+
ADT
(n = 401)
Randomization
M
F
S
P
R
O
G
R
E
S
S
I
O
N
2nd progression-
free survival(PFS2)
Metastasis-freesurvival
(primary end point)
2:1
(N = 1207)
Smith MR, et al. N Engl J Med. 2018 Feb 8 [Epub ahead of print]
1
SPARTAN ─ Phase 3 Placebo-Controlled,
Randomized International Study
NCT01946204
• The study was conducted at 332 sites in 26 countries in North America, Europe and Asia Pacific regions
13. Primary End Point
Metastasis-free survival (MFS): Time from randomization to first evidence of BICR-
confirmed radiographically detectable distant metastasis (bone or soft tissue) or death
whichever comes first
Secondary End Points
Time to metastasis (TTM): Time from randomization to first evidence of BICR-confirmed
radiographically detectable bone or soft tissue distant metastasis (does not include death)
Progression-free survival (PFS): Time from randomization to first documentation of
BICR-confirmed radiographic progressive disease or death due to any cause (whichever
occurs first); includes all local and distant radiographicprogression
Symptomatic progression: Time to skeletal-related event (SRE), pain progression or
worsening of disease-related symptoms requiring initiation of a new systemic anticancer
therapy, or development of clinically significant symptoms due to loco-regional tumor
progression requiring surgery or radiation therapy
Exploratory End Point
Progression-free survival with the first subsequent therapy (PFS2): Time from
randomization to investigator-assessed disease progression after first subsequent
treatment for mCRPC or death
Smith MR, et al. N Engl J Med. 2018 Feb 8 [Epub ahead of print]
Definition of End Points
BICR, blinded independent central review.
14. Primary Endpoint: Metastasis-free Survival
72% risk reduction of distant progression or death
The final analysis for MFS was performed after distal metastasis or death was observed in 378
patients, in 23% and 48% of patients in the APA and PBO groups, respectively
The median MFS was 40.5 months in the APA group and 16.2 months in the PBO group
Among patients who developed metastases, 60.5% in the APA group and 54.4% in the PBO group
had bone metastases
, 40.5 mo (median)
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
16.2 mo
(median)
15. Consistent MFS Benefit Across All Subgroups
The treatment effect of APA was consistently favorable across prespecified subgroups
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
16. Secondary End Point: Progression-free Survival
Patients in the APA group had a 71% risk reduction of local progression, distant progression, or
death
14.7 mo
(median)
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
, 40.5 mo (median)
17. Secondary End Point: Time to Symptomatic Progression
Patients in the APA group had a 55% risk reduction of SREs, pain progression/ worsening
symptoms, or clinically significantsymptoms
, NR
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
, NR
18. Secondary End Point: Overall Survival
Patients in the APA group had a 30% risk reduction ofdeath
, NR
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
39.0 mo
(median)
19. Secondary End Point: Time to Initiation of Cytotoxic
Chemotherapy
Patients in the APA group had a 56% risk reduction in initiation of cytotoxic chemotherapy
, NR
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
, NR
20. Summary of Prespecified Secondary End Points
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
APA
(n = 806)
PBO
(n = 401)
Hazard Ratio
(95% CI)
P Value
Secondary end points Months
Median time to metastasis 40.5 16.6 0.27 (0.22–0.34) < 0.001
Median progression-free
survival
40.5 14.7 0.29 (0.24–0.36) < 0.001
Median time to symptomatic
progression
NR NR 0.45 (0.32–0.63) < 0.001*
Median overall survival NR 39.0 0.70 (0.47–1.04) 0.07†
Median time to cytotoxic
chemotherapy
NR NR 0.44 (0.29–0.66) -
APA was associated with improvements in all secondary end points
*Crossed O’Brien-Fleming efficacy boundary (OBF) of 0.00008. † Did not cross OBF.‡ Test not done due to OS not crossing the
OBF
21. Exploratory End Point: Second Progression- free Survival
Patients in the APA group had a 51% risk reduction of second progression (PSA, radiographic,
symptomatic, or anycombination)
, NR
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
39.0 mo
(median)
22. Patients in the APA group had a 94% risk reduction in PSA progression
Exploratory End Point: Time to PSA Progression
, NR
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
3.7 mo
(median)
23. Patients in the APA group showed 90% PSA response compared to 2% in the placebo group
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
Exploratory End Point: PSA response
24. Summary of Most Common Adverse Events
24Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
Adverse Event*† APA (n = 803) PBO (n = 398)
All Gr 3/4 All Gr 3/4
no of patients (%)
Fatigue 244 (30.4) 7 (0.9) 84 (21.1) 1 (0.3)
Hypertension 199 (24.8) 115 (14.3) 79 (19.8) 47 (11.8)
Skin rash 191 (23.8) 42 (5.2) 22 (5.5) 1 (0.3)
Diarrhea 163 (20.3) 8 (1.0) 60 (15.1) 2 (0.5)
Nausea 145 (18.1) 0 63 (15.8) 0
Weight loss 129 (16.1) 9 (1.1) 25 (6.3) 1 (0.3)
Arthralgia 128 (15.9) 0 30 (7.5) 0
Fall 125 (15.6) 14 (1.7) 36 (9.0) 3 (0.8)
*AEs listed at ≥15% in either group up to 28 days after last dose. Adverse events of interest do not necessarily
meet the ≥15% criterion in either group.
† Incidences when adjusted for exposure (events per 100 patient-years) in the apalutamide and placebo
groups, respectively, were:
• fatigue (32.3 vs. 27.2)
• hypertension (36.3 vs. 38.7)
• skin rash (29.6 vs. 8.3)
• diarrhea (21.6 vs. 22.6)
• nausea (15.8 vs. 20.4)
• weight loss (18.3 vs. 10.5)
• arthralgia (14.7 vs. 8.0)
• fall (13.6 vs. 10.0).
25. Summary of Adverse Events of Interest
25Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
Other AEs of interest APA (n = 803) PBO (n = 398)
All Gr 3/4 All Gr 3/4
no of patients (%)
Fracture 94 (11.7) 22 (2.7) 26 (6.5) 3 (0.8)
Dizziness 75 (9.3) 5 (0.6) 25 (6.3) 0
Hypothyroidism 65 (8.1) 0 8 (2.0) 0
Mental impairment
disorders‡
41 (5.1) 0 12 (3.0) 0
Seizures 2 (0.2) 0 0 0
‡ Includes any of the following adverse events: disturbance in attention, memory impairment, cognitive disorder, or
amnesia.
26. Conclusions
26
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
Apalutamide was associated with a 30% reduction in risk of
death at this early interim analysis for survival (p = NS)
Apalutamide resulted in a 51% risk reduction in PFS2 even in
the face of a high rate of subsequent approved treatment in
the placebo group
Patient-reported outcomes indicate maintained overall health-
related quality of life with the addition of apalutamide to
androgen-deprivation therapy
Consistent improvements in secondary and exploratory end
points provide support for the veracity of the primary finding
27. Conclusions
Smith MR, et al. N Engl J Med. 2018 Apr 12;378(15):1408-1418.
Apalutamide was associated with a 30% reduction in risk of
death at this early interim analysis for survival (p = NS)
Apalutamide resulted in a 51% risk reduction in PFS2 even in
the face of a high rate of subsequent approved treatment in
the placebo group
Patient-reported outcomes indicate maintained overall health-
related quality of life with the addition of apalutamide to
androgen-deprivation therapy
Consistent improvements in secondary and exploratory end
points provide support for the veracity of the primary finding