Soft Tissue Sarcoma: Can We Refine The Approach?
1) Soft tissue sarcomas are a heterogeneous group of cancers accounting for 1% of malignancies with over 50 histological subtypes and poor outcomes for metastatic disease.
2) The PALETTE trial found that treatment with pazopanib resulted in a median progression-free survival of 20 weeks compared to 7 weeks for placebo, representing a 65% reduction in risk of disease progression or death.
3) Subgroup analyses showed benefit of pazopanib across patient characteristics including number of prior therapies. Pazopanib was generally well-tolerated with mainly grade 1-2 adverse events.
Management of Early Breast Cancer (by Dr. Akhil Kapoor)Akhil Kapoor
Comprehensive discussion on Management of Early Breast Cancer along with NCCN guidelines.
Slides prepared by Dr. Akhil Kapoor
(Resident, Department of Radiation Oncology,
Acharya Tulsi Regional Cancer Treatment & Research Institute, Bikaner, Rajasthan, India
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Management of Early Breast Cancer (by Dr. Akhil Kapoor)Akhil Kapoor
Comprehensive discussion on Management of Early Breast Cancer along with NCCN guidelines.
Slides prepared by Dr. Akhil Kapoor
(Resident, Department of Radiation Oncology,
Acharya Tulsi Regional Cancer Treatment & Research Institute, Bikaner, Rajasthan, India
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
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.
Similar to Soft Tissue Sarcoma, Can we refine the approach (20)
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.
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
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.
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.
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.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
1. Soft Tissue Sarcoma:
Can We Refine The Approach?
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University ACOD 2015 – Novartis Symposium
Helnan Palestine – 22/10/2015
2. Member of Advisory Board, Consultant, and Speaker for:
● Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen
Cilag, Merck Serono, Novartis, Pfizer
Speaker Disclosures:
3. Fast Statistics & Challenges:
• 1% of all malignancies.
• More than 50 histopathological subtypes.
• Local Control is 75 – 80% after definitive surgery.
• 5 Year OAS 50% (Death From Metastases).
• 5 Year OAS (Isolated Operable Lung Deposits) 25%.
• Median survival = 12 months for metastatic disease.
• Grouped as 1 disease for many decades.
4. Improvement of Disease Specific
Survival: “DSS”
Proper
Surgery
Radiation
Therapy
Systemic
Therapy
Improvement in Local Control Eradication of Micrometastases
5. Sensitivity of STS to Systemic Agents:
● Very Sensitive:
Ewing/PNET, RMS, Desmoblastic Small Round Cell Tumor, GIST,
DFSP, Angiosarcoma, Myxoid/Round Cell Sarcoma, Synovial,
Leiomyosarcoma.
● Intermediately Sensitive:
MFH, Fibrosarcoma, MPNT, Hemangiopericytoma, Solitary Fibrous
Tumor, Heamgioendothelioma.
● Minimally Sensitive:
Extraskeletal Myxoid Chondrosarcoma, Epithelioid Sarcoma,
Dedifferentiated Liposarcoma, Perivascular Epithelioid Cell
Sarcoma.
● Resistant Histologies:
Alveolar Soft Part Sarcoma, Clear Cell Sarcoma, Melanoma of Soft
Parts, Conventional Chondrosarcoma, GI Leiomyosarcoma
6. High Risk Patients:
• High Grade Lesions.
• Large Tumors > 5 cm.
• Deep Lesions.
• Recurrent Tumors at Presentations.
• Leiomyosarcoma & PNST.
• Positive Margins.??
Van Glabbeke M, et al. J Clin Oncol. 1999;17:150
8. Classical Management for Non
Metastatic Disease:
• R0 Resection is the only curative management.
• Adjuvant Radiation Therapy:
1. High Grade Lesions.
2. Intermediate Grade with Positive Margins.
3. Low Grade Lesions with Positive Margins.
4. Recurrent Tumors.
5. Retroperitoneal Disease.
Local
Recurrence
10%
Amputation
Rate 5%
75% of All Patients with Localized Extremity STS will not Relapse
After Effective Local Treatment.
No Need For Further Therapy
9. • Neo-adjuvant + Surgery vs Surgery:
No Survival Advantage.
(Gortzak et al, Eur J Cancer; 2001)
• Neo-adjuvant vs Adjuvant:
No Superiority
(DeLaney et al, Int J Oncol Biol Phys; 2003).
Neo-Adjuvant Chemotherapy:
11. Updated Results with Adjuvant
Chemotherapy:
Therapy Local
Recurrence
ARR (95%CI)
Distant
Recurrence
ARR (95%CI)
Any
Recurrence
ARR (95%CI)
Survival
ARR (95%CI)
A 3% 9% 9% 5%
AI 5% 10% 12% 11%
A or AI 4% 9% 10% 6%
Peraviz et al. Cancer. 2008;13:573
Treatment Related Toxicity
13. Trials of Doxorubicin + Ifosfamide in
Metastatic Disease:
Dose (AI) Number RR %
50/5000/m2(a) 258 25
60/7500/m2(b) 88 34
75/5000/m2(c) 104 45
75-90/10000/m2(d) 79 65
(a) Santoro et al. JCO. 1995;13:1537.
(b) Edmonson et al. JCO. 1993;11:1269.
(c) Steward et al. 1993. JCO.11.15.
(d) Patel et al. Expert Opin Investig Drugs. 2000;9:1545.
• Growth Factor Support
• Treatment Related Toxicity
14. Metastatic STS: Other Regimens:
Soft Tissue Sarcoma Regimen
General Doxorubicin Single Agent.
Doxorubicin, Ifosfamide, Mesna (AIM)
Doxorubicin, Dacarbazine (AD)
Mesna, Doxorubicin, Ifosfamide, Mesna (MAID)
Gemcitabine, Docetaxel.
Gemcitabine, Vinoralbine.
Leiomyosarcoma Doxorubicin, Gemcitabine, Dacarbazine
Gemcitabine, Docetaxel
Myxoid Liposarcoma Anthracyclines
Trabectedin
Ifosfamide
G III Liposarcoma Ifosfamide
Angiosarcoma Paclitaxel or Docetaxel or Liposomal Doxorubicin
Desmoid Tumor Doxorubicin based or Methotrexate or Vinblastine or
Tamoxifen.
15. Soft Tissue Sarcoma:
Biological Key Players & Possible Targets
Characteristic Chromosomal
Translocation
Complex
Karyotypes
• Overexpression of Growth Factors
• Upregulation of Biological Cascades
++ Angiogenesis
Mahaling et al. Targeting sar- comas: novel biological agents and future perspectives. Curr Drug
Targets. 2009;10:937–49.
Soft Tissue Sarcoma
• High Grade
• Advanced Disease
• Metastases
16. Tyrosine Kinase Receptors
VEGFR - 1 VEGFR - 2 VEGFR - 3 NRP - 1 NRP - 2
VEGFs
VEGF - A VEGF - B VEGF - C VEGF - D PlGF
Soft Tissue Sarcoma:
Biological Key Players & Possible Targets
17. VEGF
R
AKT
Grb SOS
mTOR
Protein Synthesis
HIF-1@
Metabolism
Growth
Angiogenesis
RAS
RAF
Mek
Erk
Cell Cycle Progression &
Proliferation
1. Avastin [package insert]. South San Francisco, CA: Genentech; 2009. 2. Escudier B et al; TARGET Study Group. N Engl J
Med. 2007;356:125-134. 3. Escudier B et al. J Clin Oncol. 2009;27:3312-3318. 4. Nexavar [package insert]. Wayne, NJ: Bayer
Healthcare Pharmaceuticals; 2007.
Bevacizumab
Everolimus
Soft Tissue Sarcoma:
Biological Key Players & Possible Targets
18. Soft Tissue Sarcoma:
Biological Key Players & Possible Targets
Kumar R et al. Mol Cancer Ther 2007;6:2012; Sonpavde G & Hutson TE. Curr Oncol Rep 2007;9:115;
GlaxoSmithKline. VOTRIENT® (pazopanib) SPC. 2012; 4. Kumar R et al. Br J Cancer 2009;101:1717.
Significant Anti-Angiogenic Effect
19. Matching placebo
(n=123)
Registration trial; PALETTE phase III:
Study design
Disease assessment
• At week 4, 8, 12, 20 and at 8-week intervals thereafter
VOTRIENT* (800 mg QD)
(n=246)
Secondary
endpoints
Primary
endpoint
OS
ORR
QoL
Safety
TTR
DoR
PFS by
independent
review
(RECIST v 1.0)
2:1n=369
R
A
N
D
O
MI
Z
E
DoR, duration of response; ORR, overall response rate; PFS, progression-free survival; QoL, quality of life;
QD, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; TTR, time to response
*Until disease progression, unacceptable toxicity, withdrawal of consent for any reason or death
Van Der Graaf W et al. Lancet 2012;19:1879)
20. PALETTE: Included/excluded histological
subtypes
Included:1,2
● Fibroblastic
● Fibrohistiocytic
● Leiomyosarcoma
● Synovial sarcoma
● Malignant peripheral nerve sheath
tumours
● Sarcoma not otherwise specified (NOS)
● Vascular STS
● Malignant glomus tumours
20
References: 1. Van Der Graaf W et al. Lancet 2012;19:1879; 2. Van Der Graaf W et al. ASCO 2011; abstract LBA10002: oral presentation.
Excluded:1,2
• Adipocytic sarcoma
• Osteosarcoma
• Inflammatory myofibroblastic sarcoma
• Chondrosarcoma
• Dermatofibrosarcoma protuberans
• Mixed mesodermal uterine tumour
• GIST
• Mesothelioma
• Ewing’s sarcoma/PNET
• Non-alveolar and non-pleiomorphic
rhabdomyosarcoma
21. PALETTE: Patient demographics
PLACEBO
(n=123)
PAZOPANIB
(n=246)
Age
Median (years) 51 56
Range (years) (18–78) (20–83)
Performance status
(WHO)
0 60 (49%) 118 (48%)
1 63 (51%) 128 (52%)
Histology (by central
pathology or local if
unavailable)
Leiomyosarcoma 49 (40%) 109 (44%)
Synovial sarcoma 13 (11%) 25 (10%)
Other type 61 (49%) 112 (46%)
Grade at initial
diagnosis (local)
I / low 3 (2%) 24 (10%)
II / intermediate 30 (24%) 63 (26%)
III / high 90 (73%) 159 (65%)
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
22. PALETTE: Prior systemic therapies
PLACEBO (n=123) PAZOPANIB (n=246)
Prior (neo)adjuvant therapy 45 (37%) 74 (30%)
Prior systemic
therapy for
advanced disease
1st line 110 (89%) 232 (94%)
2nd line 67 (54%) 132 (54%)
3rd line 28 (23%) 51 (21%)
4th line 9 (7%) 16 (7%)
Including: Doxorubicin 121 (98%) 242 (98%)
Ifosfamide 93 (76%) 164 (67%)
Gemcitabine 42 (34%) 85 (35%)
Docetaxel 35 (28%) 69 (28%)
Trabectedin 22 (18%) 38 (15%)
mTOR inhibitor(s) 3 (2%) 11 (4%)
22
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
23. PALETTE: Median PFS nearly 3 times
greater than placebo at 20 weeks
REGULATORY
ANALYSIS
PLACEBO
(n=123)
VOTRIENT
(n=246)
Median PFS (weeks) 7.0 20.0
Median PFS (months) 1.6 4.6
Hazard ratio (95% CI) 0.35 (0.26, 0.48); p<0.001
CI, confidence interval; PFS, progression-free survival
1.0
Placebo
VOTRIENT
Time since randomization (weeks)
Estimatedsurvivalfunction
0.8
0.6
0.4
0.2
0.0
0 20 40 60 80 100
24. PALETTE: Progression-free survival
according to subgroup
24
Hazard ratio (95% CI)
Favours
pazopanib
Favours
placebo
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
Primary analysis (n=369)
Prior lines 0/1 (n=162)
Prior lines 2+ (n=207)
WHO PS 0 at baseline (n=178)
WHO PS 1 at baseline (n=191)
Recruited from US (n=43)
Recruited from Europe and Australia (n=245)
Recruited from Japan and Korea (n=81)
Leimoyosarcoma (n=158)
Other STS histology (n=173)
Synovial sarcoma (n=38)
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
25. PALETTE: Progression-free survival by
prior lines of treatment
Number of prior
lines of therapy
Median PFS (weeks),
95% CI
Hazard ratio,
95% CI p valuePlacebo Pazopanib
0/1
(n=162)
7.6
(4.3, 9.1)
24.7
(19.6, 27.4)
0.31
(0.19, 0.50)
<0.001
2+
(n=207)
6.1
(4.3, 8.1)
18.9
(11.9, 20.1)
0.39
(0.26, 0.57)
<0.001
Stratified log rank test and Pike estimator, independent reviewer, adjusted for WHO PS
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
26. PALETTE: Overall survival
26
REGULATORY ANALYSIS
PLACEBO
(n=123)
PAZOPANIB
(n=246)
Median OS (weeks) 46.5 54.8
Hazard ratio (95% CI) 0.87 (0.67, 1.12); p=0.256
CI, confidence interval; OS, overall survival
Placebo
Pazopanib
1.0
0.0
0.2
0.4
0.6
0.8
Estimatedsurvivalfunction
0 5 10 15 20 25 30 35
Time since randomization (months)
Reference: GlaxoSmithKline. VOTRIENT® (pazopanib) SPC. 2014; Sharma S et al. BMC Cancer 2013;13:385. Additional file 4.
27. PALETTE: Summary of best confirmed
response by independent review
● The median time to response* by independent review in the
pazopanib arm was 8.4 weeks (95% CI 4.7, 19.1)
● Median duration of response was 38.9 weeks (95% CI 16.7,
40.0) for pazopanib in the responder population
27
PLACEBO
(n=123)
PAZOPANIB
(n=246)
Response rate (complete
response + partial response)
0 (0%) 11 (4%)
Partial response 0 (0%) 11 (4%)
Stable disease 33 (27%) 134 (54%)
Progression 76 (62%) 66 (27%)
* Time to response was defined as the time from the start of treatment until the first documented evidence of complete response or partial response, whichever status was
recorded first
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
28. PALETTE: Adverse event overview
28
PLACEBO
(n=123)
PAZOPANIB
(n=240)*
On-therapy AEs by maximum grade
All Grades 110 (89%) 237 (99%)
Grade 3 23 (19%) 118 (49%)
Grade 4 7 (6%) 23 (10%)
Grade 5 4 (3%) 8 (3%)
All SAEs† 29 (24%) 99 (41%)
Fatal SAEs† 6 (5%) 8 (3%)
Discontinuations due to AEs‡ 3 (2%) 41 (17%)
Discontinuations due to drug-related AEs 1 (<1%) 34 (14%)
On-therapy treatment-related AEs (all grades) 78 (63%) 219 (91%)
AE, adverse event; SAE, serious adverse event
* Six patients (pazopanib arm) were excluded from safety population as they did not begin investigational product.
† Includes off therapy SAEs
‡ Primary reason for discontinuation
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
29. PALETTE: Newly identified serious
adverse events
ON-THERAPY AND
POST-THERAPY
ADVERSE EVENTS
PLACEBO
(n=123)
PAZOPANIB
(n=240)
Any
grade Grade 3 Grade 4
Any
grade Grade 3 Grade 4
Myocardial dysfunction* 6 (5%) – – 21 (9%) 3 (1%) 1 (<1%)
Venous thromboembolic
events
† 3 (2%) 1 (<1%) 2 (1%) 13 (5%) 5 (2%) 1 (<1%)
Pneumothorax – – – 8 (3%) – 1 (<1%)
SAEs with a higher incidence in the pazopanib-treated aSTS population
than in the pazopanib-treated aRCC population
29
* Grouping of MedDRA terms, including left ventricular dysfunction, cardiac failure, restrictive cardiomyopathy and
pulmonary oedema
† Fatal pulmonary embolus occurred in two of 240 patients treated with pazopanib
GlaxoSmithKline. Data on File. Study VEG110727. 2011. Available at: http://www.gsk-clinicalstudyregister.com
30. PALETTE*:Health-related quality of life
(HRQoL)
Patients receiving treatment with Pazopanib did not experience a clinically
meaningful or statistically significant deterioration in HRQoL compared with
placebo (p=0.291)1,3
Adapted from Sharma S et al. 2013 - Additional file 4.2
HRQoL was measured using the EORTC QLQ-C30 Global Health Status/HRQoL score
†For EORTC QLQ-C30, data were collected at baseline, week 4, week 8 and week 12.4
MID: Minimally important difference, 5 to 10. SE: Standard error. ITT: Intention to treat
1. van der Graaf W et al. Lancet 2012; 379: 1879-1886; supplementary appendix published online; 2. Sharma S et al. BMC Cancer 2013; 13: 385. Additional
file 4; 3. Sharma S et al. BMC Cancer 2013; 13: 385; 4. FDA Oncology Drug Advisory Committee Briefing Document, March 2012. Available at
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM296303.pdf(Accessed
February 2015)
*Phase III study excluded selective STS subtypes such as GIST and adipocytic sarcoma
Pazopanib (n=246)
Placebo (n=123)
Change from baseline in health-related quality of life (HRQoL, ITT population) 1,2†
31. Take Home Message:
● Soft-tissue sarcoma (STS) is a rare disease that encompasses over
50 separate histological subtypes with varying sensitivity to systemic
treatment
● Although Ifosfamide and doxorubicin remain important treatment
options in STS, therapy is increasingly tailored towards different
histological subtypes
● In post-Imatinib era; Targeted therapies such as tyrosine kinase
inhibitors will become increasingly important as we further define the
molecular basis of sarcomagenesis.
● Pazopanib is a recently approved option for advanced refractory STS
with significant prolongation of PFS and perfect compliance.
● Clinical trials remain a challenge due to the rarity and heterogeneity of STS
and international collaboration is critical to achieve high quality clinical trials
stratified by histological subtype.