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
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.
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.
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.
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 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.
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.
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.
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):
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma pre...Virotherapist
Phase 3 data from the OPTiM study in melanoma with talimogene laherparepvec presented as part of a talk on oncolytic immunotherapy at The Eighth International Conference on Oncolytic Virus Therapeutics, Oxford, UK,9-13 April 2014.
Presentación realizada por la Dra. Pilar Escudero del HCU Lozano Blesa, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.
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.
This is NHL clinical update on 57th ASH Annual Meeting and Exposition (December 5-8, 2015).
It includes only clinical aspects include both chemotherapy and antibody therapy.
BK virus has become a serious issue in hematopoietic stem cell transplantation recipients, commonly manifesting as hemorrhagic cystitis, which can last from a matter of days to months and, if severe enough, may result in death. Patients with BK virus-associated hemorrhagic cystitis often experience poor quality of life, severe pain and discomfort, and prolonged hospitalizations. Despite numerous advances in stem cell transplantation methods, BK virus-associated hemorrhagic cystitis is difficult to control and treatment options are few. This ppt provides an overview of BK virus along with risk factors, current treatment modalities
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
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.
3. 3
a mPFS values measured from beginning of chemotherapy (ie, day of randomization) to the first disease progression and, thereafter, from one progression to the subsequent
one or to death.
L, line; mPFS, median progression-free survival; PFS, progression-free survival.
Hanker LC, et al. Ann Oncol. 2012;23(10):2605-12.
mPFS
10.2 mo
(95% CI: 9.6–10.7)
mPFS
6.4 mo
(95% CI:
5.9–7.0)
mPFS
5.6 mo
(95% CI:
4.8–6.2)
mPFS
4.4 mo
(95% CI:
3.7–4.9)
mPFS
4.1 mo
(95% CI:
3.0–5.1)
mPFS
18.2 mo
(95% CI: 17.3–19.1)
5L 6L
4L
3L
2L
1L
Fourth
Recurrence
Fifth
Recurrence
Third
Recurrence
Second
Recurrence
First
Recurrence
Note: Data depict historical
mPFS of watch-and-wait,
and do not represent PFS
observed with
maintenance treatment.
The Unmet Need
~80%
Median PFS decreases after every recurrence:
5. gBRCA and sBRCA mutation in Ca Ovary
5
Approximately
40%
of patients with BRCAm OC may have no
relevant family history2,3
Approximately
20%
of OC patients a gBRCAm1,
while an additional
5-9%
may have a sBRCAm2
1. Alsop K, et al. J Clin Oncol 2012; 30:2654-63 2. Pal T, et al. Cancer 2005; 104:2807-16 3. Vergote I, et al. Eur J Cancer 2016; 69:127-34 4. Kwong A, et al. Asia-Pac J Clin Oncol, 2019; 1-12; 4. Susana Beatriz Goncalves, et al.
Journal of Clinical Oncology 2019 37:15_suppl, e17050-e17050
The use of family history, age and histology type alone for patient selection in BRCAm testing would miss a
significant proportion of cases.4 Offering gBRCA test may also miss significant sBRCAm population.
Approximately
29%
of OC patients
Harbour
tBRCAm
19. VELIA/GOG-3005: PFS in ITT Patient
Population (Regardless of HRD or BRCA
Mutation Status)
Slide credit: clinicaloptions.com
CT + Veliparib Veliparib CT + Placebo Placebo
Events, n/N (%) 191/382 (50.0) 237/375 (63.2)
Median PFS, mos (95%
CI) 23.5 (19.3-26.3) 17.3 (15.1-19.1)
Coleman. ESMO 2019. Abstr LBA3. Reproduced with permission.
0
20
40
60
80
100
PFS(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44
382
375
352
356
337
340
329
328
308
297
275
260
253
236
228
202
208
172
192
153
172
143
153
119
111
84
95
70
76
55
55
36
38
21
26
16
19
10
7
3
2
0
1 0
HR: 0.68 (95% CI: 0.56-0.83; P < .001)
Mos From Randomization
Combination Maintenance
Veliparib
throughout
Control
Patients at Risk, n
20. Maintenance Niraparib After Initial
Therapy for Ovarian Cancer (PRIMA):
Phase III Study Design
Double-blind, randomized, placebo-controlled phase III trial
Primary endpoint: PFS by BICR
Hierarchical testing in patients with HRD (HR benefit: 0.5) followed by the overall patient population
(HR benefit: 0.65)
Key secondary endpoint: OS; other secondary endpoints: PFS2, TFST, patient-reported
outcomes, safety
Patients with newly diagnosed
advanced ovarian cancer with CR or PR
following first-line platinum-based CT;
high-grade serous or endometroid
pathology; stage III with residual
disease, stage IV, or inoperable
(N = 730)
Niraparib 200-300* mg QD
(n = 484)
Placebo
(n =244)
Stratification by 1L platinum CT,
CR/PR to 1L therapy, HRD status
Tx for 36 mos or
until PD
*Initiated treatment with 300 mg QD for patients ≥ 77
kg and with platelets ≥ 150,000/μL, 200 mg QD for
patients < 77 kg and/or with platelets < 150,000/μL.
González-Martin. ESMO 2019. Abstr LBA1.
25. Phase II Study 19 of Olaparib Maintenance in
Platinum-Sensitive Recurrent Ovarian Cancer
Primary endpoint: PFS (RECIST 1.0)
Secondary endpoints: OS, safety, tolerability
Exploratory endpoints: time to first subsequent therapy or death, time to
second subsequent therapy or death
Patients with platinum-sensitive,
recurrent high-grade serous
ovarian cancer; ≥ 2 prior
platinum-based regimens with
CR/PR to most recent platinum-
based therapy; stable CA-125
(N = 265)
Treatment until
disease
progression
Olaparib
400 mg BID PO
(n = 136)
Placebo
BID PO
(n = 129)
Ledermann. NEJM. 2012;366:1382.
26. Study 19 :PFS
Ledermann. NEJM. 2012;366:1382.
HR: 0.35 (95% CI: 0.25-0.49; P < .001)
Treatment
Number of Patients
With Event (%)
Median PFS,
Mos
Olaparib 60 (44.1) 8.4
Placebo 93(72.1) 4.8
Olaparib
Placebo
Mos
150 3 6 9 12
1.0
0.8
0.6
0.4
0.2
0
ProbabilityofPFS
Patients at Risk, n
Olaparib
Placebo
136
129
104
72
51
23
23
7
6
1
0
0
33. Olaparib for the maintenance treatment of PSR OC1-3
Phase III study3
Recurrent BRCAm ovarian cancer after two prior lines of
platinum therapy (n=295)
Maintenance in patients achieving a CR/PR on
platinum therapy
Olaparib tablets PO 300mg BID
Olaparib significantly prolonged PFS compared with placebo
(HR 0.30; 95% CI 0.22 to 0.41; p<0.0001)
Study 19
Phase II study1,2
Recurrent ovarian cancer after two or more prior lines of
platinum therapy (n=265)
Maintenance in patients achieving a CR/PR on
platinum therapy
Olaparib capsules PO 400mg BID
Olaparib significantly prolonged PFS compared with placebo
(HR 0.35; 95% CI 0.25 to 0.49; p<0.00001)
Trend towards benefit for overall survival (HR of 0.73; 95% CI
0.55 to 0.95; nominal p=0.025; statistical significance not reached)
Improvements in PFS and OS were also seen in the non-BRCAm
subgroup (HR 0.54 [95% CI 0.34 to 0.85], p=0·0075; and HR 0.83
[95% CI 0.55 to 1.24], nominal P=0.37; respectively)
BID=twice daily; BRCAm=BRCA1/2 mutation; CI=confidence interval; CR=complete response; HR=hazard ratio; non-BRCAm=no mutations in BRCA1/2; OC=ovarian cancer; OS=overall survival;
PFS=progression-free survival; PO=orally; PR=partial response; PSR=platinum-sensitive relapsed
1. Ledermann J, et al. N Engl J Med. 2012;366(15):1382–1392; 2. Ledermann J, et al. Lancet Oncol. 2016;17(11):1579–1589; 3. Pujade-Lauraine et al. Lancet Oncol. 2017;18(9):1274–1284
40. “
”
Health-related Quality of Life and Patient-
Centred Outcomes With Olaparib Maintenance
After Chemotherapy in Patients With Platinum-
Sensitive, Relapsed Ovarian Cancer and a
BRCA1/2 Mutation (SOLO2/ENGOT Ov-21): A
Placebo-Controlled, Phase 3 Randomized Trial
MICHAEL FRIEDLANDER 1, VAL GEBSKI 2, EMMA GIBBS 2, LUCY DAVIES 3, RALPH BLOOMFIELD 4, FELIX HILPERT 5, LARI B WENZEL 6, DANIEL EEK 7, MANUEL
RODRIGUES 8, ANDREW CLAMP 9, RICHARD T PENSON 10, DIANE PROVENCHER 11, JACOB KORACH 12, TOMASZ HUZARSKI 13, LAURA VIDAL 14, VANDA
SALUTARI 15, CLARE SCOTT 16, MARIA ORNELLA NICOLETTO 17, KENJI TAMURA 18, DAVID ESPINOZA 2, FLORENCE JOLY 19, ERIC PUJADE-LAURAINE
42. SOLO2: Quality-Adjusted PFS
Olaparib
(n = 185)
Placebo
(n = 94)
Difference
(95% CI)
P Value
Mean PFS, mos 17.55 8.94 8.61
(6.47 to 10.87)
< .0001
Mean utility (mixed model) 0.80 0.81 -0.02
(-0.05 to 0.02)
.284
QAPFS, mos 13.96 7.28 6.68
(4.98 to 8.54)
< .0001
43. SOLO2: Time Without Symptoms of Disease or Toxicity
• TWiST duration
significantly
longer with
olaparib vs
placebo
Duration, Mos Olapari
b
(n =
185)
Placeb
o
(n = 94)
Differen
ce
(95% CI)
P Value
TWiST 13.5 7.21 6.29
(2.95-
8.58)
< .0001
Toxicity 3.69 0.71 2.98
(1.52-
4.68)
.0002
45. March 30 - April 2, 2014
Sheraton Sonoma County
Petaluma, California
Treatment
PFS
Median
(95% CI)
(Months)
Hazard Ratio
(95% CI)
p-value
% of Patients
without
Progression or
Death
12 mo 18 mo
Niraparib
(N=138)
21.0
(12.9, NE) 0.27
(0.173, 0.410)
p<0.0001
62% 50%
Placebo
(N=65)
5.5
(3.8, 7.2)
16% 16%
Mirza MR et al. N Engl J Med 2016; Presidential Symposium, ESMO 2016
ENGOT-OV16 / NOVA:PFS:gBRCA+
46. BRCAwt
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression
or Death
12 mo 18 mo
Niraparib
(N=71)
9.3
(5.8, 15.4) 0.38
(0.231,
0.628)
p=0.0001
45% 27%
Placebo
(N=44)
3.7
(3.3, 5.6)
11% 6%
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression
or Death
12 mo 18 mo
Niraparib
(N=35)
20.9
(9.7, NR) 0.27
(0.081,
0.903)
p=0.0248
62% 52%
Placebo
(N=12)
11.0
(2.0, NR)
19% 19%
sBRCAmut
Treatment
PFS
Median
(95% CI)
(Months)
Hazard
Ratio
(95% CI)
p-value
% of Patients
without
Progression or
Death
12 mo 18 mo
Niraparib
(N=92)
6.9
(5.6, 9.6) 0.58
(0.361,
0.922)
p=0.0226
27% 19%
Placebo
(N=42)
3.8
(3.7, 5.6)
7% 7%
HRD-positive HRD-negative
Mirza MR et al. N Engl J Med 2016; Presidential Symposium, ESMO 2016
ENGOT-OV16 / NOVA:PFS in Non-Germline BRCA mutant
47. *CR (defined by RECIST v1.1) or PR (defined by RECIST v1.1 and/or a GCIG CA-125 response [CA-125 within normal range]) maintained until entry to ARIEL3 (≤8 weeks of last dose of
chemotherapy). †ATM, ATR, ATRX, BARD1, BLM, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MRE11A, NBN, PALB2, RAD50,
RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RPA1.
ARIEL3: Rucaparib in Relapsed Ca Ovary
• HRR status by NGS mutation analysis
BRCA1 or BRCA2
Non-BRCA HRR gene†
None of the above
• Response to recent platinum
CR
PR
• Progression-free interval after
penultimate platinum
6 to <12 months
≥12 months
Patient eligibility Stratification
• High-grade serous or endometrioid
epithelial OC, primary peritoneal, or
fallopian tube cancers
• Sensitive to penultimate platinum
• Responding to most recent platinum
(CR or PR)*
Excludes patients without assessable
disease following second surgery
• CA-125 within normal range
• No restriction on size of residual tumour
• ECOG PS ≤1
• No prior PARP inhibitors
Placebo
BID
n=189
Rucaparib
600 mg BID
n=375
Randomisation2:1
5
0