The document summarizes the current state of metastatic breast cancer treatment. It discusses how survival rates have improved over time and metastatic breast cancer is now considered a chronic, treatable disease rather than an immediately terminal condition. Treatment involves systemic therapies like chemotherapy, endocrine therapy, targeted therapies, as well as radiation, surgery, and supportive care. Selection of optimal first-line systemic treatment depends on disease characteristics and patient factors. Ongoing research focuses on tailoring and sequencing treatments to overcome resistance and further extend patient survival and quality of life.
Despite remarkable progress in the treatment of breast cancer in recent years, management of estrogen receptor (ER)-positive disease remains a challenge. Through didactic and case presentations, expert faculty will address clinical debates regarding optimal treatment selection and the incorporation of new classes of targeted therapies into practice to improve outcomes and overcome resistance in the management of ER-positive breast cancer
Target Audience
This activity has been designed to meet the educational needs of medical oncologists and other healthcare providers who are involved in the care and treatment of patients with advanced estrogen receptor (ER)-positive breast cancer.
Purpose
The goal is to optimize the clinical decision-making of clinicians involved in the treatment of advanced ER-positive breast cancer by providing updates on emerging data.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply.
More information:
http://imeronline.com/864dsd
Tratamiento inicial de pacientes posmenopáusicas con cáncer de mama HR+/her2-...Mauricio Lema
Versión 2 (definitiva): Presentado en la Clínica VIDA en 11.11.2016, por invitación de Jairo Estrada. Versión corregida (se corrigen errores en 3 diapositivas de la versión anterior).
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
Join Dr. Erica Mayer, medical oncologist at Dana-Farber/Brigham and Women's Cancer Center, to learn about exciting metastatic breast cancer developments from the past year. Dr. Mayer presents an overview on metastatic breast cancer and the subgroups, including Hormone Receptive, HER2+, and Triple Negative, and highlights recent advances for each of these subgroups. She also discusses the importance of clinical trials and what it means to participate in a clinical trial.
For more information on the Breast Cancer Treatment Center at Dana-Farber Cancer Institute, please visit:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx
Learn about the latest research and treatment for ER+ breast cancer. Erica Mayer, MD, MPH, medical oncologist with the Susan F. Smith Center for Women's Cancers, discusses new clinical trials and treatment options for this subset of breast cancer patient.
This presentation was originally given on Oct. 17, 2015, at the Metastatic Breast Cancer Forum, hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, in Boston, Mass.
Learn more: http://www.susanfsmith.org
Despite remarkable progress in the treatment of breast cancer in recent years, management of estrogen receptor (ER)-positive disease remains a challenge. Through didactic and case presentations, expert faculty will address clinical debates regarding optimal treatment selection and the incorporation of new classes of targeted therapies into practice to improve outcomes and overcome resistance in the management of ER-positive breast cancer
Target Audience
This activity has been designed to meet the educational needs of medical oncologists and other healthcare providers who are involved in the care and treatment of patients with advanced estrogen receptor (ER)-positive breast cancer.
Purpose
The goal is to optimize the clinical decision-making of clinicians involved in the treatment of advanced ER-positive breast cancer by providing updates on emerging data.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of August 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply.
More information:
http://imeronline.com/864dsd
Tratamiento inicial de pacientes posmenopáusicas con cáncer de mama HR+/her2-...Mauricio Lema
Versión 2 (definitiva): Presentado en la Clínica VIDA en 11.11.2016, por invitación de Jairo Estrada. Versión corregida (se corrigen errores en 3 diapositivas de la versión anterior).
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
Join Dr. Erica Mayer, medical oncologist at Dana-Farber/Brigham and Women's Cancer Center, to learn about exciting metastatic breast cancer developments from the past year. Dr. Mayer presents an overview on metastatic breast cancer and the subgroups, including Hormone Receptive, HER2+, and Triple Negative, and highlights recent advances for each of these subgroups. She also discusses the importance of clinical trials and what it means to participate in a clinical trial.
For more information on the Breast Cancer Treatment Center at Dana-Farber Cancer Institute, please visit:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx
Learn about the latest research and treatment for ER+ breast cancer. Erica Mayer, MD, MPH, medical oncologist with the Susan F. Smith Center for Women's Cancers, discusses new clinical trials and treatment options for this subset of breast cancer patient.
This presentation was originally given on Oct. 17, 2015, at the Metastatic Breast Cancer Forum, hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, in Boston, Mass.
Learn more: http://www.susanfsmith.org
Adjuvant Systemic Therapy | Lunch and Learn - Dec 2014 | Dr. Caroline LohrischCBCFBCYukon
Dr. Lohrisch's research presentation is about a multi-disciplinary approach to treatment therapies that will assist oncologists in choosing the right treatment, for the right woman, for the right disease.
Learn more about her research http://ow.ly/Fzfdt
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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.
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/
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Integrating Ayurveda into Parkinson’s Management: A Holistic Approach
T. Cufer - Breast cancer - State of the art for advanced breast cancer
1. Metastatic Breast
Cancer Treatment:
State of the Art
Tanja Cufer, MD, PhD
University Clinic Golnik
Medical Faculty, Ljubljana
EORTC BCG, Chair
ESO Masterclass; Amman 2011
2. Metastatic Breast Cancer (MBC)
The survival of pts with
5-year survival of MBC pts in
metastatic disease is Slovenia
improving
MBC is still: 20
18
Incurable but highly 16
treatable 14 1980-85
1986-90
Chronic disease 12
Survival (%)
1990-95
10
The goal of treatment: 8
1996-00
2000-05
Control of symptoms 6
4
Prolongation of life
2
Good quality of life 0
3. Multidisciplinary Treatment Modalities
in MBC
Systemic therapy
Endocrine therapy
Chemotherapy
Targeted systemic therapy
Radiotherapy (bone, CNS mets)
Surgery (solitary lesions)
Supportive therapy (bisphosphonates)
Palliative medicine
5. Tailoring Systemic Therapy in MBC
Disease-related factors
Biology of disease
ER/PR status
HER2 status
Proliferation
Disease-free interval
Tumor burden (number & site of mets)
Need for rapid disease control
Previous systemic therapy
Patient-related factors
PS
Age
Co-morbidities
Patient’s preferences
6. Individualized Treatment Selection
HER2 Endocrine responsive Endocrine non-responsive
(HR+, long DFI, soft (HR-/uncertain, short DFI,
ER tissue/bone mets) visceral mets)
HER2- ET CT
negative
HER2- positive HER2 directed + ET HER2-directed + CT
Thargeted therapies comes first!
8. ASCO 2010: Significant Rate of Discordance
Between Primary and Metastases
#1007 #CRA 1008 #1009
Studies Amir et al. Locatelli et al. Karlsson et al.
N=271 N=255 N=477
prospective retrospective retrospective
(liver)
Would you deny a(12%) 22/197 (11%) 123/336 (36%)
ER+ primary with loss in recurrence 21/174 patient a targeted
ER- primary with gain in recurrence 8/57 (14%) 15/58 (25%) 32/141 (22%)
treatment due to changes in the 32%
Overall ER discordance rate 12% 14.5%
Overall PR discordance ratemetastatic site? 48%
34% 43%
HER2- primary with gain in recurrence 9/197 (4.6%) 7/118 (5.9%) n.d.
HER2+ primary with loss in recurrence 3/24 (12.5%) 17/54 (31.5%) n.d.
Change in management from results of 15% 12% n.d.
recurrence biopsy
Discussion ASCO 2010: Richardson AL
9. Endocrine Therapy for MBC
Premenopausal patients
Tamoxifen
OAS
OAS +Tamoxifen
OAS + AI
Postmenopausal patients
Als
Tamoxifen
Fulvestrant
10. Combined Tamoxifen and LHRH Agonist vs LHRH
Agonist Alone in Premenopausal Advanced Breast
Cancer: A Meta-Analysis of Four Randomized Trials
End Point LHRH agonist LHRH agonist HR 95%CI p
alone + Tamoxifen
N=256 N=250
Median survival, years 2.5 2.9 0.78 0.63-0.96 0.02
Median PFS, months 5.4 8.7 0.70 0.58-0.85 0.0003
Objective response % 29.7 38.8 0.67 0.46-0.96 0.03
LHRH+TAM
LHRH
Klijn, et al. J Clin Oncol 2000;19.
11. Randomized Phase III Trials of AIs vs.
Tamoxifen as First-line Treatment of
Postmenopausal MBC
Anastrozole1 Anastrozole2 Letrozole3 Exemestane4
No. patients 170 vs 182 340 vs 328 453 vs 454 182 vs 189
ORR, % 21 vs 17 33 vs 33 32 vs 21* 46 vs 31*
CBR, % 59 vs 46* 56 vs 56 50 vs 38* 66 vs 49*
TTP or PFS, months 11 vs 6* 8 vs 8 9 vs 6* 10 vs 6*
ER status unknown, % 11 vs 11 56 vs 54 34 vs 33 15 vs 11
ORR = overall response rate; CBR = clinical benefit rate; TTP = time to progression; PFS = progression free survival; ER = estrogen receptor
*Statistically significant difference
1. Nabholtz JM, et al. J Clin Oncol. 2000;18 2. Bonneterre J, et al. J Clin Oncol. 2000;18
3. Mouridsen H, et al. J Clin Oncol. 2003;21 4. Paridaens R, et al. J Clin Oncol. 2008;26
12. Hormonal Therapy in Postmenopausal
MBC: Aromatase Inhibitors
All three AIs showed higher RR and longer TTP compared to
Tam in first line setting; no differences in long term OS
(Mouridsen et al JCO 2003; Bonneterre et al Cancer 2001,
Paridaens et al, ASCO 2004);
All three AIs seem to be equally effective with slight
differences in untoward effects (Rose et al ASCO 2002,
Cameron et al , ASCO 2004, Mayordomo et al, ASCO 2006)
The efficacy of AIs after Tam is comparable to the efficacy of Tam
after AIs (Thurlimann et al, EJCancer 2003)
Steroid inactivator exemestane is effective after failure to
nonsteroidal AIs, nonsteroidal AIs are effective after failure to
exemestane (Thurlimann et al, EJCancer 1997, Bertelli G, et al.
Oncology. 2005)
13. FIRST: Fulvestrant 500 mg vs. Anastrozole
as First-Line
1.0
Proportion of patients alive
and progression-free
0.8 Fulvestrant 500 mg
Anastrozole 1 mg
0.6
0.4
0.2 HR = 0.66 (95% CI: 0.47-0.92)
P = .01
0.0
0 6 12 18 24 30 36 42 48
Time (months)
Number of patients at risk:
Fulvestrant 500 mg 102 74 65 52 45 34 20 6 0
Anastrozole 1 mg 103 69 55 39 30 21 8 2 0
CI = confidence interval; HR = hazard ratio; TTP = time to progression
Robertson JF, et al. Cancer Res. 2010;70: Abstract S1-3.
14. How to Overcome Resistance to ET ?
mTORC1 activates ER in a
ligand-independent fashion1
Estradiol suppresses
apoptosis induced by
PI3K/mTOR blockade2
Hyperactivation of the
PI3K/mTOR pathway is
observed in endocrine-
resistant breast cancer cells3
mTOR is a rational target to
enhance the efficacy of
hormonal therapy
1. Bjornsti MA, et al. Nat Rev Cancer. 2004;4(5):335-348. 2. Crespo JL, et al. Microbiol Mol Biol Rev. 2002;66(4):579-591.
3. Huang S, et al. Cancer Biol Ther. 2003;2(3):222-232. 4. Mita MM, et al. Clin Breast Cancer. 2003;4(2):126-137.
5. Wullschleger S, et al. Cell. 2006;124(3):471-484. 6. Johnston SR. Clin Cancer Res. 2005;11(2 Pt 2):889S-899S.
15. TAMRAD: Tamoxifen +/- Everolimus as
Second- Line After AIs Failure
1.0
0.9
Probability of survival
0.8
0.7
0.6
0.5
0.4 TAM
TAM + RAD
0.3
0.2 Hazard Ratio (HR) = 0.32 (95% CI: 0.15-0.68)
Exploratory log-rank: P = .0019
0.1
0.0
0 3 6 9 12 15 18 21 24 27 30 33 36
Months
Patients at risk:
TAM + RAD: n = 54 53 51 49 49 45 38 26 14 6 0
TAM: n = 57 55 53 50 44 38 30 22 9 4 0
CI = confidence interval; HR = hazard ratio; RAD = RAD001; TAM = tamoxifen
Bachelot T, et al. Cancer Res. 2010;70: Abstract S1-6.
16. BOLERO-2: Exemestane +/- Everolimus
in AI Refractory Disese
N = 724
Everolimus 10 mg/day + PFS
Exemestane 25 mg/day
Postmenopausal (N = 485)
2 OS
ER+ HER2- ABC
ORR
refractory to
1 Bone Markers
letrozole or Placebo + Safety
anastrozole Exemestane 25 mg/day PK
(N = 239)
Stratification:
Sensitivity to prior hormonal therapy
Presence of visceral disease
No crossover
ABC: advanced breast cancer, NSAI: non steroidal aromatase inhibitors, HER2-: human epidermal growth factor receptor 2 – negative;
PFS: progression-free survival; PK: pharmacokinetics
Baselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.
17. BOLERO-2 Primary Endpoint: PFS
Local Assessment
HR = 0.43 (95% CI: 0.35–0.54)
100
Log rank P value = 1.4 x 10 -15
80 EVE + EXE: 6.9 months
Probability of Event, %
PBO + EXE: 2.8 months
60
40
20
Everolimus + Exemestane (E/N = 202/485)
Placebo + Exemestane (E/N = 157/239)
0
0 6 12 18 24 30 36 42 48 54 60 66 72 78
Time, weeks
No. of Patients Still at Risk:
Everolimus 485 398 294 212 144 108 75 51 34 18 8 3 3 0
Placebo 239 177 109 70 36 26 16 14 9 4 3 1 0 0
Baselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.
18. Chemotherapy for MBC
Combination Chemotherapy or Sequential Use of
Monotherapy?
Most trials and meta-analysis compare single agent vs.
combination and NOT sequential use of single agents
vs. combination CT.
The majority of trials show that combination CT yields
higher RR, in some higher PFS, higher toxicity and no or
quite small survival benefit.
19. Chemotherpy Agents = Survival Gains
Pooled analysis of 6 consecutive trials of first-line CT in MBC:
- Clear evidence of an increase in OS during the past 20 years,
starting with the inclusion of paclitaxel
100
90
80
1998-2001
70 Median OS
Probability %
1995-1997
60 1992-1994 - 18.0 mos, in 1983-1986
50
1987-1989 - 17.2 mos, in 1987-1989
1983-1986
40
- 19.2 mos, in 1992-1994
30
- 26.1 mos, in 1995-1997
- 23.6 mos, in 1998-2001 cohorts
20
(P for heterogeneity .0001)
10
0
0 1 2 3 4 5 6 7 8
Years
CT, chemotherapy; OS, overall survival
Gennari A, et al. Cancer. 2005;104(8):1742-1750.
20. Randomized Studies with Crossover Following
in the Monotherapy Arm
Time to Overall
Author Comparison Number of Response Rate Progression Survival
Year (x number of cycles) patients (%) (months) (months)
Alba A x 3 Doc x 3 144 61 10.5 22.3
2004 A + Doc x 6 51 9.2 21.8
Beslija Doc X 100 40 7.7 19.0
2006 Doc + X 68* 9.3* 22.0*
Conte E x 4 Pac x 4 202 58 10.8‡ 26.0
2004 E + Pac x 8 58 11.0‡ 20.0
Koroleva Doc x 4 A x 4 193 56 6.9 13.8
2001 A + Doc x 8 49 6.7 11.9
A + Doc║ x 8 59 8.3 14.5
Sjöstrom Doc 238 42* 6.3* 10.4
1999 MF 21 3.0 11.1
Sledge A 739 36 5.8¶ 18.9
2003 Pac 34 6.0¶ 22.2
A + Pac 47* 8.0*¶ 22.0
Soto X Pac or Doc 368 45 8.4‡ 31.5
2006 X + Pac 64* 6.7‡ 33.1
X + Doc 75* 8.1‡ 28.5
Tomova Doc x 4 G x 4 100 28 6.7 15.9
2008 Doc + G x 8 31 7.0 15.5
*Denotes statistically significant result with P≤.05
Cardoso F, et al. J Natl Cancer Inst. 2009;101(17):1174-1181
21. COMBINATION SEQUENTIAL SINGLE AGENTS
>RR Similar survival ! <Toxicity
Faster symptom/disease control Better overall QoL
Better management of resources
22. New Cytotoxic Agents
New cytotoxic agents
Targeting microtubules: Eribulin, Epothilones
“Old” agents in new formulations
Capecitabine (considered standard in A&T pretreated pts)
Liposomal anthracyclines
New formulations of anti-microtubules: albumin bound, nab-
paclitaxel
“Old” agents in new indications
Platinum & Alkylating agents for TN
23. EMBRACE: A Phase III Study of Eribulin in
Heavily Pre-treated pts: Overall Survival (ITT)
1.0
1-Year Survival
Eribulin (n = 508) 53.9%
0.8 TPC (n = 254) 43.7%
Survival Probability
Eribulin
median 13.12 months
0.6
TPC HR* 0.81 (95% CI: 0.66, 0.99)
0.4 median 10.65 months P value† = 0.041
0.2
2.47 months
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Overall Survival, months
Twelves C, et al. J Clin Oncol. 2010;28(15s): Abstract CRA1004.
24. What is the optimal duration of
chemotherapy ?
25. U1
Results: Progression Free Survival
Optimal Duration of Study Longer better Shorter better %Weight HR 95%CI
Coates 1987 13 0.56 0.44-0.71
Chemotherapy? Harris 1990
Muss 1991
2
3
1.18
0.26
0.65-2.15
0.16-0.43
Ejlertsen 1993 28 0.71 0.61-0.83
Gregory 1997 10 0.70 0.53-0.92
Falkson 1998 5 0.46 0.31-0.68
Bastit 2000 11 0.65 0.50-0.84
Nooij 2003 8 0.67 0.50-0.90
Gennari 2006 6 1.01 0.71-1.43
Majordomo 2009 8 0.77 0.57-1.05
Alba 2010 6 0.53 0.37-0.76
Overall 100 0.64
0.66 0.55-0.76
0.60-0.72
U1 0.10 1.00 10.00
Results: Overall Survival Test for heterogeneity, p=0.001 Test for treatment effect, p<0.001
Study Longer better Shorter better %Weight HR 95%CI
Coates 1987 13 0.79 0.62-1.01
Harris 1990
Muss 1991
2
5
1.06
1.11
0.57-1.97
0.74-1.67
Longer CT duration:
Ejlertsen 1993
Gregory 1997
17
5
0.78
0.81
0.63-0.97
0.54-1.21
36% reduction in the risk of
Falkson 1998 8 0.94 0.69-1.28 progression (HR 0.64; 95%
Bastit 2000
Nooij 2003
18
17
0.96
1.03
0.78-1.18
0.83-1.27
CI 0.55 – 0.76)
Gennari 2006
Majordomo 2009
4
7
1.12
0.94
0.73-1.72
0.67-1.32
9% reduction in the risk of
Alba 2010 5 0.86 0.58-1.27 death (HR 0.91; 95% CI 0.84-
Overall
0.10 1.00 10.00
100 0.91 0.84-0.99
0.99)
Test for heterogeneity, p=0.69 Test for treatment effect, p=0.044
25
Gennari et al, ESMO 2010
26. Targeted Therapies in MBC
HER2-directed therapy (considered standard
in HER2+ disease)
PARP inhibitors
Antiangiogenic agents
27. Anti-HER2 Therapy in Combination with
Chemotherapy in HER2-Positive MBC
TTP OS
Trial Treatment ORR (%)
(months) (months)
Slamon et al.1; Trastuzumab + 7.1 vs. 25.1 vs.
49 vs. 17*
Smith et al. 2 paclitaxel vs. paclitaxel 3.0* 18.0*
Trastuzumab + 11.7 vs. 31.2 vs.
Marty et al.3 61 vs. 34*
6.1* 22.7*
docetaxel vs. docetaxel
Di Leo et al. 4
Lapatinib + paclitaxel 8.5 vs. 24.0 vs.
(ErbB2+ 63 vs. 38*
vs. paclitaxel 5.8* 19.8*
patients only)
Lapatinib + paclitaxel 9.7 vs. 27.8
Guan et al. 5 69 vs. 50*
6.5* vs.20.5*
vs. Paclitaxel
*= statistically significant
1. Slamon et al. N Engl J Med 2001;344, 2. Smith et al. Anticancer Drugs 2001;12 Suppl 4:S3–10, 3. Marty et al. J
Clin Oncol 2005;23, 4. Di Leo et al. Clin Oncol 2008;26, 5. Guan et al. 33rd SABCS 2010; Abstract P3-14-24
28. First-line Treatment with Trastuzumab +
Docetaxel or Vinorelbine in ErbB2+ MBC:
HERNATA Study
Anderssen M, et al. J Clin Oncol 2011;29
29. Anti-HER2 Therapy in Combination with
Endocrine Therapy in ER+/HER2+ MBC
Anastrozole + Trastuzumab (TANDEM)1
CB 28 v 43%; PFS 2.4 v 4.8 months
Letrozole + Lapatinib (EGF30008)2
CB 29 v 48%; PFS 3.0 v 8.2 months
1. Kaufman, et al. J Clin Oncol 27 2009, 2. Johnston, et al. J Clin Oncol 27 2009,
30. TANDEM: Evaluation of Anastrozole +/-
Trastuzumab in HER2+/HR+ MBC
100 A A+H
Outcome P Value
(n = 104) (n = 103)
Progression-Free
80 Events, n 99 87
Survival (%)
60 Median PFS, mos
2.4 (2.0-4.6) 4.8 (3.7-7.0) .0016
(95% CI)
40
20
0
0 5 10 15 20 25 30 35 40 45 50 55 60
2.4 months Months
A+H n = 103 48 31 17 14 13 11 9 4 1 1 0 0
A n = 104 36 22 9 5 4 2 1 0 0 0 0 0
Kaufman, et al. J Clin Oncol 2009.
31. TANDEM: Evaluation of Anastrozole +/-
Trastuzumab in HER2+/HR+ MBC
Anastrozole
N=207
Anastrozole +
Median age 55 years Trastuzumab
Visceral disease 1/3
Prior chemo 1/2
Cross-over 70%
6,8% Response rate 20,3%
p 0.0016
2,4m Median PFS. 4,8m
23,9m Median O.S. 28,5m
32,1m Median O.S. 41,9m
if no liver mets p 0.03
Trastuzumb added to anastrozole RR, PFS (and possibly OS if no liver mets)
IMPORTANCE OF STARTING BIOLOGICAL AGENT SOON
Mackey, et al. SABC 06;abst.03. Adapted from M. Piccart
32. Current Evidence Based Options of Anti-
HER2 Treatment Beyond Trastuzumab
Progression (Phase III trials)
Continuing trastuzumab (GBG 26 / BIG 3-05
study)
Lapatinib + capecitabine (EGF100151 study)
Lapatinib + trastuzumab (EGF104966 study)
33. Comparison of Three Prospective Phase III
Trials on Anti-HER2 Treatment Beyond
Trastuzumab Progression
GBG-26a EGF100151b EGF104900a
(n=156) (n=399) (n=296)
Regimen XH X XL X LH L
ORR, % 48 27 32 17 10 7
TTPc
HR 0.69 (p=0.03) 0.72 (p=0.01) 0.73 (p=0.01)
Median, 8.2 5.6 5.5 4.2 2.8 1.9
months
OS
HR 0.76 (p=0.26) 0.78 (p=0.18) 0.74 (p=0.02)
Median, 25.5 20.4 15.6 15.3 14.0 9.5
months
aVon Minckwitz et al 2008; O’Shaughnessy et al 2008;
bInvestigator Assessment, US Lapatinib Prescribing Information & Cameron et al 2008;
34. New HER2-directed Agents
Pertuzumab (first-in-class ErbB dimerisation inhibitor)
Phase 2 trials completed, undergoing phase 3 in combination with
trastuzumab (CLEOPATRA trial)
Neratinib (oral, pan-ErbB TKI)
Phase 2 trials in monotherapy and in combination with paclitaxel or
vinorelbine completed, undergoing phase III combination trial with
paclitaxel (NEFERTT trial)
Afatinib (oral irreversible ErbB1 and 2 inhibitor)
Phase III trial in combination with vinorelbine (Lux-Breast1)
Trastuzumab - DM1 (HER2-targeted antibody-drug
conjugate)
In phase2 trial comperable efficacy with better toxicity profile
compared to trastuzumab and docetaxel
Ongoing phase 3 trials
35. TDM4450g : Progression-Free Survival
Median Hazard Log-rank
PFS, mos ratio 95% CI P value
Trastuzumab
1.0
+ docetaxel (n=70) 9.2 0.364–
0.594 .0353
Proportion Progression-Free
T-DM1 (n=67) 14.2 0.968
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8 10 12 14 16 18 20
Time, months
Number of patients at risk
T+D 70 66 63 53 43 27 12 4 2 2 0
T-DM1 67 60 51 46 42 35 22 15 6 3 0
Hazard ratio and log-rank P value were from stratified analysis.
Hurvitz S, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract 5001.
37. Bevacizumab: First-Line MBC Meta
Analysis
E2100
Paclitaxel
RANDOMIZE
Chemo + Optional
Previously Treat Second-line
AVADO No BV
Untreated Chemo + BV
Docetaxel until (AVADO and
MBC Chemo + PD RIBBON-1
BV only)
RIBBON-1
Capecitabine,
Taxane,
or
Anthracycline
O’Shaugnessy J, et al. J Clin Oncol. 2010;28(15S): Abstract 1005.
38. Bevacizumab in MBC
RIBBON-1:
E21001 AVADO2 Capecitabine3 RIBBON-1: A/T3
Placebo (Pl) controlled No Yes Yes Yes
q 3 wk
Weekly
Chemotherapy q 3 wk docetaxel (D) Capecitabine (C) docetaxel/nabPAC/FA
paclitaxel (P)
C/EC/FEC
10 mg/kg 7.5 or 15 mg/kg 15 mg/kg 15 mg/kg
Dose of bevacizumab (B)
q 2 wk q 3 wk q 3 wk q 3 wk
P P+B D+PI D+B C+PI C+B A/T+PI A/T+B
ORR 25% 49% 49% 55%/63% 24% 35% 38% 51%
PFS, months 5.9 11.8 80 8.7/8.8 5.7 8.6 8.0 9.2
0.79 (7.5 mg)
0.60 P = .0318 0.69 0.64
HR
P<.0001 0.72 (15 mg) P = .0002 P<.0001
P = .0099
OS, months 25.2 26.7 NR NR 21.2 29 23.8 25.2
0.88 0.92 (7.5 mg) 0.85 1.03
HR
P = .16 0.86 (15 mg) P = .27 P = .83
Meta-Analysis (O’Shaughnessy et al ASCO 2010)
PFS: 2.5 months, OS: 0.3 months
1.Miller K, et al. N Eng J Med. 2007;357(26), 2. Miles D, et al. J Clin Oncol. 2008;26:(May 20 Suppl): Abstract
LBA1011, 3. Robert NJ, et al. J Clin Oncol. 2009;27(15S): Abstract 1005.
39. Multi-center, Randomized Open-label Phase
III RegistrationNTrial of Iniparib in mTNBC
= 519
Patient Population:
mTNBC Gem/Carbo (GC) Crossover allowed
0–2 prior chemo for (N= 258)
metastatic TNBC to GCI following
Gemcitabine 1000 mg/m2 IV d 1, 8 Disease Progression*
Stable CNS metastases Carboplatin AUC2 IV d 1, 8 (central review)
allowed
21-day cycles
Stratification: R
No prior chemo vs 1–2 Gem/Carbo + Iniparib (GCI)
prior chemo for mTNBC
(N= 261)
Gemcitabine - 1000 mg/m2 IV d 1, 8
Carboplatin - AUC2 IV d 1, 8
Endpoints: Iniparib - 5.6 mg/kg IV d 1,4,8,11
Primary: OS, PFS
21-day cycles
Secondary: ORR,
safety/tolerability
96% (n=152) of progressing patients crossed over to GCI at time of primary analysis
O’Shaughnessy et al, ASCO 2011
41. Potential Solutions to Improve MBC
Outcome
New treatments
New strategies with “old” treatments
More pts in clinical trials
Less than 5-10% of cancer patients participate in
clinical trials in the western countries!!
Biomarkers (predictive, pharmacogenetics,
pharmacogenomics…)
International RECOMMENDATIONS (that are
followed!) (implementation of recommendations
such as St Gallen increased survival EBC)