This presentation discusses breast cancer, specifically hormone receptor positive/HER2 negative breast cancer. It provides statistics on the distribution of breast cancer molecular subtypes in the United States. It also discusses the evolving treatment landscape for hormone receptor positive metastatic breast cancer, including the approvals and use of targeted therapies in combination with endocrine therapy, such as CDK4/6 inhibitors. Clinical trial results are summarized that demonstrate improved progression-free survival when a CDK4/6 inhibitor is added to first-line endocrine therapy for advanced hormone receptor positive breast cancer. An approach to personalized therapy is proposed based on factors such as endocrine sensitivity and molecular alterations.
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
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.
SHARE Webinar: Latest Research on Metastatic Breast Cancer from SABCS 2015bkling
Dr. Tiffany Traina, medical oncologist at Memorial Sloan-Kettering Cancer Center, presents the latest research on metastatic breast cancer reported at the San Antonio Breast Cancer Symposium in December 2015.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
The Trial Assigning IndividuaLized Options for Treatment (Rx) -TAILORx,TAILORx clinical trial showed that most women with hormone receptor (HR)–positive, HER2-negative, axillary node–negative early-stage breast cancer and a mid-range score on a 21-tumor gene expression assay (Oncotype DX® Breast Recurrence Score) do not need chemotherapy after surgery
Never-smoker with Lung cancer in Southern California. Never-smokers with lung cancer have distinct genetic changes. Chao Family Comprehensive Cancer Center at UCI Irvine offers cutting edge clinical trials. Please call 1-714-456-8000
Adjuvant Endocrine Therapy For Postmenopausal Breast CancerEmad Shash
Questions Covered in the presentation:
• Should patients receive an AI or Tamoxifen?
• Should patients receive monotherapy (AI or Tamoxifen alone) or sequential
therapy using both?
• 5 vs 10 years of therapy?
• If More than 5 years of endocrine therapy, which class to be used
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
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.
SHARE Webinar: Latest Research on Metastatic Breast Cancer from SABCS 2015bkling
Dr. Tiffany Traina, medical oncologist at Memorial Sloan-Kettering Cancer Center, presents the latest research on metastatic breast cancer reported at the San Antonio Breast Cancer Symposium in December 2015.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
Dr. Jennifer Mueller, gynecologic cancer surgeon at Memorial Sloan Kettering Cancer Center, will share research updates on uterine/endometrial cancer and other new developments in treatment and surgery.
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
The Trial Assigning IndividuaLized Options for Treatment (Rx) -TAILORx,TAILORx clinical trial showed that most women with hormone receptor (HR)–positive, HER2-negative, axillary node–negative early-stage breast cancer and a mid-range score on a 21-tumor gene expression assay (Oncotype DX® Breast Recurrence Score) do not need chemotherapy after surgery
Never-smoker with Lung cancer in Southern California. Never-smokers with lung cancer have distinct genetic changes. Chao Family Comprehensive Cancer Center at UCI Irvine offers cutting edge clinical trials. Please call 1-714-456-8000
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
Changing landscape in the treatment of advanced prostate cancer Alok Gupta
This presentation describes how the treatment of stage 4 prostate cancer has improved over last 100 years. This was presented at URO ONCOLOGY UPDATE meeting of Delhi Urological Society on 18th March 2017
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
7. Evolving Treatment Landscape of HR-Positive MBC
SOC regimens for metastatic HR+/HER2- BC based on endocrine tx
Tamoxifen
(Selective ER
modulator)
1970-80
AIs
Anastrozole
Exemestane
Letrozole
1990s
Fulvestrant
(Selective ER
degrader)
2002
Fulvestrant HD
2010
Everolimus
(mTOR inhibitor)
2012
Palbociclib
(CDK4/6 inhibitor)
2015-17
Ribociclib,
Abemaciclib
(CDK4/6 inhibitors)
2017-18
Targeted Therapy + ET
.
Approvals
8. Initial Treatment of HR+, HER2- Advanced Breast Cancer
Majority of patients with HR+,
HER2- metastatic BC should be
treated with endocrine therapy–based
regimens often in combination with
targeted therapies
‒ Chemotherapy is not recommended
unless patients have progressed
through multiple lines of endocrine
therapy or display signs of visceral
crisis
Treatment considerations
‒ Sites and extent of disease
‒ Organ function
‒ Prior systemic therapy
‒ Length of disease-free interval
‒ Rate of disease progression
‒ Presence of gBRCA1/2 mutation
9. TREATMENT GUIDELINES FOR HR+, HER2– ADVANCED
BREAST CANCER
ESMO1 In HR+, HER2– disease, endocrine therapy is the treatment of first choice independent of
metastatic site, unless rapid response is needed. Limited visceral metastases are not a
contraindication for endocrine therapy
ABC2 Endocrine therapy is the preferred option for HR+ disease, even in the presence of visceral
disease, unless there is concern or proof of endocrine resistance or rapidly progressive
disease needing a fast response
ASCO3 Endocrine therapy should be recommended as initial treatment for patients with HR+
metastatic breast cancer except in patients with immediately life-threatening disease or
in those with rapid visceral recurrence on adjuvant endocrine therapy.
NCCN4 Endocrine therapy recommended unless there is visceral crisis, or progression with no
clinical benefit after 3 sequential endocrine therapy regimens.
3
11. CHEMOTHERAPY VERSUS ENDOCRINE THERAPY
1
Wilcken et al, Cochrane System Database Review 2009
No significant differences in overall survival.
12. Combining Targeted and Antiestrogen Therapies to
Overcome Resistance in HR+ Advanced Breast Cancer
~ 50% of advanced HR+
BCs are de novo
resistant to ET, with
most developing
acquired resistance
Mechanisms of
resistance may include
loss or alteration of
ER expression;
overexpression or
activation of growth
factor receptors; or
activation of
downstream signal
transduction pathways
PI3K
Akt
PTEN
mTOR
RAS
Raf
MEK
MAPK
ER Target Gene
Transcription
P P
EGFR
HER2
E
E
ER
E
ER
E
ER
E
TKI
mTOR Inhibitors
Everolimus
Aromatase Inhibitor
Nonsteroidal AIs:
Anastrozole
Letrozole
Steroidal AI:
Exemestane
Selective ER
Modulators
Tamoxifen
Toremifene
ER Downregulator
Fulvestrant
CDK4/6 Inhibitors
Palbociclib
Abemaciclib
Ribociclib Cell
Cycle
Transcription
Silencing
13. G2
S
M
G1
pRB
The Role of CDK4/6 in Breast Cancer
Growth of HR+ MBC is
dependent on cyclin D1, a direct
transcriptional target of ER
Cyclin D1 activates CDK4/6,
resulting in G1-S phase
transition and cell cycle entry[1]
Some cell-line models of
endocrine resistance show
dependence on cyclin D1 and
CDK4/6[2,3]
ERα Mitogenic
signaling
S phase transcription
program
G1/S transition
P P P
pRB
E2F
E2F
CDK1
Cyclin B
CDK1/2
Cyclin A
CDK2
Cyclin E
CDK4/6
Cyclin D
14. pRB
Cyclin D1 and CDK4/6 Drive Cellular Proliferation
Downstream of Signaling Pathways
Lange. Endocr Relat Cancer. 2011;18:C19. Kundsen. Trends Cancer. 2017;3:39. Otto. Nat Rev Cancer.
2017;17:93. Corona. Drug Des Devel Ther. 2018.12:321. Tripathy. Clin Cancer Res. 2017;23:3251-3262.
Gene
transcription
G2 S
M G1
Inactive
Active tumor
suppressor
E2F
E2F
Restriction point
p16
p21
p53
CDK4/6
Cyclin D
CDK2
Cyclin E
pRB
P P P
G0
Pl3K/Akt
STATs MAPKs
ER/PR/AR Wnt/β-catenin
NF-κB
FGFR
15. Pan-CDK Inhibitors: Early
Clinical Trial Experience
Both agents showed low therapeutic index resulting in
toxicities at doses sufficient to inhibit target CDKs
Agent Primary Targets Antitumor Activity Notable Grade 3/4
Toxicities
Alvocidib
(flavopiridol)
CDKs 1, 2, 4, 6, 7, 9 Solid tumors: minimal
CLL (relapsed/
refractory): ORR ≈ 25%
to 50%
Neutropenia,
gastrointestinal/diarrhea,
tumor lysis syndrome,
infections
Seliciclib CDKs 1, 2, 5, 7, 9 Solid tumors: minimal, if
any
Nausea, vomiting, fatigue,
hepatic dysfunction
17. PALOMA-1 PALOMA-2 MONALEESA-2 MONARCH-3 MONALEESA-3
Study design
Phase II
1st line
Phase III
1st line
Phase III
1st line
Phase III
1st line
Phase III
1st and 2nd line
Endocrine
partner Letrozole Letrozole Letrozole
Letrozole
or anastrozole
Fulvestrant
CDK4/6
inhibitor Palbociclib Palbociclib Ribociclib Abemaciclib Ribociclib
Patients, N 165 666 668 493 367
HR 0.49 0.58 0.56 0.54 0.57
PFS, mos 20.2 vs 10.2 24.8 vs 14.5 25.3 vs 16 NR vs 14.7 NR vs 18.3
ORR, % 56 vs 39 55.3 vs 44.4 52.7 vs 37.1 59 vs 44 40.9 vs 28.7*
Impact of CDK4/6 Inhibition on PFS: First-Line Setting
1
18. 18
PALOMA CLINICAL TRIALS
Footer text here. Arial 7pt font in black.
• Postmenopausal women
with HR+, HER2– ABC
• No prior treatment for
advanced disease
N = 666
PALOMA-2
2:1
PBO + LET
PAL + LET
PALOMA-2 study results
All patients
PAL+LET
(n = 444)
PBO+LET
(n = 222)
Median PFS, mo 24.8 14.5
HR (95% CI); P value
0.58 (0.46, 0.72);
< 0.001
• Pre- or postmenopausal
women with HR+, HER2–
ABC
• Relapsed/progressed
during prior ET
N = 521
PALOMA-32
2:1
PBO + FUL
PAL + FUL PALOMA-3 study results
All patients2 PAL+FUL
(n = 347)
PBO+FUL
(n = 174)
Median PFS, mo 9.5 4.6
HR (95% CI);
P value
0.46 (0.36, 0.59);
< 0.0001
19. 19
MONALEESA CLINICAL TRIALS
Footer text here. Arial 7pt font in black.
ML-2
ML-7
• Postmenopausal women
with HR+, HER2– ABC
• No prior therapy for ABC
N = 668
ML-3 • Men and postmenopausal women
with HR+, HER2– ABC
• No prior CT for ABC
N = 726
• Premenopausal women with HR+,
HER2– ABC
• No prior ET for advanced disease
• ≤ 1L prior CT allowed
N = 672
ML-2 study results
All patients
RIBO+LET
(n = 334)
PBO+LET
(n = 334)
Median PFS, mo 25.3 16.0
HR (95% CI);
P value
0.568 (0.457, 0.704);
9.63×10–8
ML-3 study results
All patients2 RIBO+FUL
(n = 484)
PBO+FUL
(n = 242)
Median PFS, mo 20.5 12.8
HR (95% CI);
P value
0.593 (0.480, 0.732);
<0.001
ML-7 study results
All patients
RIBO+ET+GOS
(n = 335)
PBO+ET+GOS
(n = 337)
Median PFS, mo 23.8 13.0
HR (95% CI);
P value
0.55 (0.44, 0.69);
<0.0001
1:1
RIBO + LET
PBO + LET
2:1
RIBO + FUL
PBO + FUL
1:1
RIBO + ET +
GOS
PBO + ET +
GOS
20. 20
MONARCH CLINICAL TRIALS
Footer text here. Arial 7pt font in black.
MONARCH-2
MONARCH-3
• Pre- and postmenopausal
women with HR+,
HER2– ABC
• Progression on ET
([neo]adjuvant or 1L
advanced)
N = 669
1:1
ABE + FUL
PBO + FUL
MONARCH-2 study results
All patients
ABE+FUL
n = 446
PBO+FUL
n = 223
Median PFS, mo 16.4 9.3
HR (95% CI);
P value
0.553 (0.449, 0.681);
<0.001
N = 493
1:1
ABE + NSAI
PBO + NSAI
MONARCH-3 study results
All patients
ABE+NSAI
n = 328
PBO+NSAI
n = 165
Median PFS, mo NR 14.7
HR (95% CI);
P value
0.54 (0.41, 0.72);
0.000021
N = 493
• Postmenopausal women
with HR+, HER2– ABC
• No prior systemic therapy
in the advanced setting
22. MONALEESA-3: OVERALL SURVIVAL BY LINE OF THERAPY
OS by line of therapy was consistent with overall population
Slamon. ESMO 2019. Abstr LBA7_PR.
RIBO + FULV PBO + FULV
Events/N 102/237 60/109
Median OS, Mos 40.2 32.5
RIBO + FULV PBO + FULV
Events/N 63/237 47/128
Median OS, Mos NR 45.1
RIBO + FULV
PBO + FULV
RIBO + FULV
PBO + FULV
237231222218213210199188184179172167158152145135
109103 98 97 93 90 88 83 81 78 77 72 69 63 61 59 54 49 35 23 15 6
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
129122 94 63 36 17 7 1 0
1 0 0
0
20
40
60
80
100
Mos
237229222217214210207206205202194190182174173166163157138 92 54 22 0
6 1
128126 122121119116113110106104 99 97 93 91 85 84 82 70 40 21 8 2 0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
Mos
0
20
40
60
80
100 First line Early relapse + Second line
OS,
%
Patients
Atrisk,n
PBO
RIBO
Patients
Atrisk,n
PBO
RIBO
HR: 0.700 (95% CI: 0.479-1.021) HR: 0.730 (95% CI: 0.530-1.004)
125
23. Approach to Therapy for HR+/HER2- MBC:
Move to Personalization
1L[1-4] 2L[1] 3L
AI + CDK4/6i Fulvestrant ±
everolimus
Exemestane +
everolimus[8]
Fulvestrant + CDK4/6i
Exemestane +
everolimus
4L/5L[1]
Taxane or
capecitabine
4L+[1]
Eribulin
PIK3CAm:
fulvestrant +
alpelisib[5]
BRCAm: olaparib or
talazoparib[9,10]
Sacituzumab
govitecan
(IMMU-132)[13]
ESR1m: SERD (+ CDK4/6i)[6,7]
HER2 low: trastuzumab
deruxtecan
(DS8201a)[11]
HER2m: neratinib[12]
24. *De novo stage IV disease appears to be enriched in relative endocrine resistant disease.
†No data comparing CDK4/6i combined with AI vs fulvestrant in first line setting.
HR+/HER2- Advanced BC: Changing Paradigms
CT
Poor Endocrine Sensitivity
Progression within 2 yrs
from start of adj ET
Fulvestrant +
CDK4/6i
High Endocrine Sensitivity
NSAI + CDK4/6i
ET naive*
Progression > 1 yr after adj ET
Fulvestrant†
(bone only, no
prior ET)
EXE + EVE
PIK3CA WT
FULV
(± EVE)
FULV +
Alpelisib
PIK3CA MUT
FULV +
CDK4/6i
EXE + EVE
Progression between 2-3 yrs from
start of or < 1 yr from end of adj ET
Moderate Endocrine Sensitivity
AI +
Alpelisib
PIK3CA WT PIK3CA MUT
EXE + EVE AI +
alpelisib
PIK3CA WT
PIK3CA MUT
25. THERAPEUTIC OPTIONS FOR HR+, HER2– ABC ARE
EVOLVING
• ET-based therapy remains the basis
of treatment for HR+, HER2– ABC1
• CDK4/6 inhibitors in combination with ET have
resulted in a paradigm shift for treating HR+,
HER2– ABC2
─ A meta analysis of 50,029 patients with HR+, HER2–
MBC across 140 phase 2 and 3 studies found that the
combination of CDK4/6 inhibitors plus hormone therapies
is associated with better PFS than standard hormone
therapies as first- or second-line treatments for
postmenopausal patients3
Oestrogen
ER
SRC
Me/Ac
EGFR/HER2/HER3
Inhibitors
FGFR
Inhibitors
IGFR
Inhibitors
EGFR/HER3 FGFR IGFR MET
E2F
CDK
Cyclin D
p21WAF1/CIP1
SRC Inhibitor
SRC
STAT3
RAF
MEK
ERK
CDK
Inhibitors
MAPK/MEK
Inhibitors
RAS PI3K
PIP2
PI3K Inhibitors
mTOR Inhibitors
PIP3
mTORC2
AKT
TSC
p53
Rheb
Rheb
mTORC1
P
AKT
Inhibitors
HDAC Inhibitors
MDM2
ER
SERDs/
SERMs
25
Editor's Notes
BC, breast cancer; TNBC, triple-negative breast cancer.
BC, breast cancer; CDK, cyclin-dependent kinases; ER, estrogen receptor; ET, endocrine therapy; HD, high dose; mTOR, mammalian target of rapamycin; SOC, standard of care; tx, therapy.
References
Anastrozole [package insert]. 2014.
Exemestane [package insert]. 2018.
Letrozole [package insert]. 2018.
Fulvestrant [package insert]. 2018.
Everolimus [package insert]. 2018.
Palbociclib [package insert]. 2018.
Ribociclib [package insert]. 2018.
Abemaciclib [package insert]. 2018.
Brufsky AM. Cancer Treat Rev. 2017;59:22-32.
Lim E, et al. Oncology (Williston Park). 2012;26:688-694.
Croxtall JD, et al. Drugs. 2011;71:363-380.
Cohen MH, et al. Oncologist. 2001;6:4-11.
BC, breast cancer; HR, hormone receptor.
AI, aromatase inhibitor; BC, breast cancer; E, estrogen; ER, estrogen receptor; ET, endocrine therapy; HR, hormone receptor; MAPK, mitogen activated protein kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; RAS, renin-angiotensin system; TKI, tyrosine kinase inhibitor.
References
Johnston SR. Clin Cancer Res. 2010;16:1979-1987.
Brufsky AM. Cancer Treat Rev. 2017;59:22-32.
AlFakeeh A, et al. Curr Oncol. 2018;25(suppl 1): S18-S27.
CDK, cyclin-dependent kinase; ER, estrogen receptor; HR, hormone receptor; MBC, metastatic breast cancer.
CDK, cyclin-dependent kinase.
CLL, chronic lymphocytic leukemia.
CDK, cyclin-dependent kinases; ET, endocrine therapy.
CDK, cyclin-dependent kinase; NR, not reached.
The MONALEESA-3 first line patient population PFS analysis was not reached