1.
Ovarian Cancer: New
Insights and Treatments
Jason D. Wright and June Y. Hou
Columbia University

2.
Ovarian Cancer
• 2015 ovarian cancer statistics
o 21,290 cases
o 14,180 deaths

3.
0%#
20%#
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80%#
100%#
0# 5# 10# 15# 20#
Stage&I&
Year&since&diagnosis&
1980#
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40%#
60%#
80%#
100%#
0# 5# 10# 15# 20#
Stage&III0IV&
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A.#
B.#
Outcomes for Ovarian
Cancer
• Survival is improving for
ovarian cancer
• 5 year survival:
o 27% (1958-1962)
o 50% (1999-2001)
• Relative survival (1975
vs. 2006):
– Stage I (HR=0.51)
– Stage III-IV (HR=0.49)

4.
Treatment of Ovarian
Cancer
• Surgery in combination with chemotherapy
• Surgery –cytoreduction (debulking)
• Neoadjuvant chemotherapy

5.
Treatment of Ovarian
Cancer
• Adjuvant chemotherapy
o IP chemotherapy
o Dose dense chemotherapy
• Chemotherapy for recurrent cancer
o New agents
o New combinations
o Precision medicine

6.
Clinical Trials in Ovarian
Cancer
Phase Study design
Phase I Safety and toxicity
Phase II Demonstrating some effect
Phase III Demonstrating superior outcome
compared to standard drug/treatment
regimen

7.
Regulatory Approval
Bast RC, Thigpen JT, Arbuck SG, et al. Gynecol Oncol 2007;107(2):173-6.

8.
Bevacizumab

9.
Olaparib

10.
Precision Medicine:
the new era for
ovarian cancer
treatment

11.
The Precision Medicine Initiative

12.
• Traditional cancer care:
One size fits all
• Works great for some
patients but not for
others
• Most medical treatments
have been designed for
the average patient
• Precision medicine:
Individualized therapy
• Takes into account
individual differences in
the genetic makeup of
patient’s disease
• Transforming the way
we treat diseases such
as cancer

13.
Precision Medicine has already transformed
the treatment of lung cancer
Survival benefit of 1.1 years was seen in patients with
an oncogenic driver mutation who received targeted
therapy compared to those without a driver mutation
or targeted treatment

14.
Applications:
Offering tailored treatment
strategies
Providing early detection
Prediction of response or
toxicity
Precision medicine can help to improve
survival in women with ovarian cancer

15.
New opportunities for
Immunotherapy
• PD1 / PDL1 inhibitors have
been granted breakthrough
FDA approval for PDL1+
bladder and NSCLC
• Early phase clinical trials
have shown promising
results for inhibitors of PD-1
and PD-L1 in recurrent
ovarian cancer patients
with low toxicity
• Clinical trials are ongoing for
combination treatments
and validation of response
PDL1+

16.
Taking advantage of the p53 mutation
• Almost all epithelial
ovarian cancers have
p53 mutations, leading to
defect in cell’s ability to
repair DNA
• Wee 1 inhibitor (AZD1775)
combined with
chemotherapy shows
promise in patients with
p53 mutated platinum-
resistant ovarian cancer

17.
Center for Precision Medicine For
Gynecologic Oncology
• Initiated fall 2014
• Comprehensive
program to integrate
genome-based
knowledge into the
treatment of
gynecologic cancers
• One of the first
programs in the
country
Histology-based to molecularly-guided treatment

18.
Ovarian Cancer clinical trials at CUMC
Setting Agent
Neoadjuvant
/ 1st line
* GOG 3005
C/T +/- ABT888
1st
recurrence
* MORAB (plat sens)
* GYN49 (plat resist)
AZD1775 + Carbo/ Gemzar or
weekly taxol
2nd
recurrence
* Janssen
Doxil vs. Yondelis + Doxil
2-3rd
recurrence
CORAIL
PM01183, PLD or topotecan
Any prior
therapy
MEK162 + Letrozole
IRB# Agent
N4003 D53032b / MDM2 inhibitor
N9701
Trastuzumab/Pertuzumab
· Erlotinib
· Vemurafenib
· Vismodegib
O0006
MGCD516
(Multi-target TKI)
O2406
INCB2430 + Nivolumab
IDO1 + PD1
O7762
Varililumab + Nivolumab
CD27+PD1
PO559
MGCD265
cMET inhibitor
MATCH / NCI 73 genes
Phase 1B-III Phase 1

19.
Precision medicine-based clinical trial

20.
Precision Medicine is the future of
clinical therapy in cancer care
• Number of agents available to target molecular
drivers in cancer is rapidly increasing
• Treatment algorithms based on molecular targets
are already improving outcomes for some patients
• The road to true ‘personalized medicine’ is not
accessible to all patients. Need to advocate and
fast track advances for ovarian cancer
• Quality of life should be an important focus

21.
Strategies for Long-Term
Management of Recurrent
Ovarian Cancer
September 10, 2015
Annie Ellis
Ovarian Cancer Survivor/Research Advocate

22.
Annie Ellis
 11-year Ovarian (2 recurrences) and 4-year Breast Cancer Survivor
 FDA Patient Representative
 CDMRP Ovarian Cancer Research Program Integration Panel
 Roswell Park Ovarian Cancer SPORE Patient Representative
 2014 AACR Scientist↔Survivor Program
 Ovarian Cancer National Alliance
◦ Research Advocate
◦ Formerly on Special Programs (Education) and Conference Committees
◦ Conference Speaker; Survivors Teaching Students®
 SHARE
◦ Helpline Peer
◦ Former Peer Support Group Facilitator
◦ Presented at SGO 2008 “The Patient’s Perspective”
 NY Presbyterian-Columbia Woman to Woman Peer
 Ovarian Cancer Research Fund: Clinical Trials Video and
Symposium Speaker
 2013 Congressional Briefing on Ovarian Cancer for Society for
Women’s Health Research (SWHR)

23.
Journal of Gynecologic Oncology, November 2014, Volume 135, Issue 2, Pages 261–265

24.
The work is not over until
everyone has a chance
to have a lasting and meaningful
Dance with NED.
No Evidence of Disease
FDA Ovarian Cancer Endpoints Workshop
Co-sponsored by FDA/SGO/AACR/ASCO
September 3, 2015
Ovarian Cancer Survivorship Survey
(August 2015)

25.
My journey
 2006 OCNA
Ovarian Cancer National
Alliance Conference
2008 SGO 
SHARE Presentation
The Patients’ Perspective

26.
Joan Sommer:
“Surviving and living with ovarian cancer is not an arbitrary
period like five years. It is an everyday thing where you
wake up, take a deep breath in spite of your fears and pain,
and find a way to take your place in the world”
“Surviving cancer is not a place you strive for in the
distance. It is here and now. You are in it. It is up to you to
be part of it, to find your hope.”
“Hope is falling asleep and
expecting to wake up each day
in spite of what you might have
heard. It is thinking about the
possibilities not probabilities.
It is preparing to die but
expecting to live.”
“When faced with uncertainty
there is nothing wrong with hope.”

27.
Coping
Images: various internet sources

28.
Coping—Professional Support
Major Depression
• Feeling sad most of the time.
• Loss of pleasure and interest in activities you
used to enjoy.
• Changes in eating and sleeping habits.
• Nervousness.
• Slow physical and mental responses.
• Unexplained tiredness.
• Feeling worthless.
• Feeling guilt for no reason.
• Not being able to pay attention.
• Frequent thoughts of death or suicide.
Cancer-related
Post-Traumatic Stress
• Repeated frightening thoughts.
• Being distracted or overexcited.
• Trouble sleeping.
• Feeling detached from oneself or reality
When to get help:
►Any time you feel you need assistance
►When mood/feelings get in the way of day to day functioning
http://www.ncbi.nlm.nih.gov/books/NBK66039/
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0032735/
Images: various internet sources

29.
Support
Various internet sources, SHARE and Robin Cohen

30.
It is a truthuniversallyacknowledged,
that a womanin possessionof
recurrentovariancancer
must bein want of
more effectivetreatments.
Adapted from Pride and Prejudice by Jane Austin.

31.
Different paths to long-term
management

32.
Exciting times!
DataInformationKnowledge
Source: Hanahan D, Weinberg RA. Hallmarks of cancer:
the next generation. Cell. 2011;144:646-674.

33.
Confusing times
http://www.gutenberg.org/

34.
Frustrating Times
Oxfordjournals.org

35.
Goals and Priorities
After we have thought about our goals and priorities, it may be
easier to decide what we are willing to do to achieve them.
One day Alice came to a fork in the
road and saw a Cheshire cat in a tree.
“Which road do I take?” she asked.
“Where do you want to go?” was his
response.
“I don’t know,” Alice answered.
“Then,” said the cat, “it doesn’t
matter.”
If you don’t know where you want to go,
any road will take you there.
http://www.alice-in-wonderland.net/resources/pictures/tulgey-wood-inhabitants/

36.
Potential benefits and potential risks

37.
Empowered Decision Making:
Important Tools for Navigation
• Current tests and scans
• Location, volume
• Pathology
• Type of tumor
• Hereditary mutation status
• Genetic testing recommended
for all ovarian cancer patients
• BRCA
• Lynch Syndrome? BROCA Panel?
• Other information
• Molecular profiling?
• Assays?
• Communication
• Open and honest dialogue
• Ask questions; Negotiate
• Plan to manage side effects
• Be your own advocate

38.
Empowered Decision Making:
Clinical Trials
• Consider using clinical trials to expand treatment options.
• Consider participating in clinical trials sooner. The fewer
lines of therapy someone has had, the more trials they
can qualify for.
• Many novel drugs and targeted therapies are paired with
approved drugs in trials. Discuss with your medical team
whether it is reasonable to delay using those particular
approved drugs to help maintain eligibility down the road.
http://www.bhdsyndrome.org/http://www.bhdsyndrome.org/http://www.crwf.com/phase-i-ii-iii-or-iv/

39.
SHARE’s Clinical Trial Matching Service
http://www.sharecancersupport.org/share-new/clinicaltrial_1/clinicaltrial/

40.
Empowered Decision Making:
Second Opinions or Consultations
• Fresh look
• More treatment options
• Clinical trials
• Different approach
• Similar patient
• Confirmation / Explanation
• Specialists
• Manage Side Effects
• Pathology
• More brains thinking about YOU!
► Plan ahead!
• Reports
• Scans
• Access to slides

41.
Choice of
Therapy
Size &
Location
Platinum
Response
Molecular
Information
Schedule
of Drugs
Cell
Type
Patient
Preference
(Hair, etc.)
Residual
Side Effects
or
Symptoms
Hereditary
Mutation
Status
Is there a clinical trial option?
Is it reasonable?
Is it available?
How does it fit with how I want to live?
Clinical
Trial
Surgery Radiation
Approved
Therapy
Adapted from GCF Survivor Course at NYU 5/15/10: Management of Recurrent Ovarian Cancer,
Matthew A. Powell, MD, Washington University School of Medicine, St. Louis, MO

42.
Staying in the game: Keep Options in
Play
http://www.vehiclehi.com/

43.
Recap: Strategies
• Be informed and be your own advocate!
• Incorporate Goals and Priorities
• Consider Clinical Trials to expand treatment options
• Second Opinions / Consultations
• Proactively Manage Side Effects
• Chemo Breaks!
• Keep Options in Play
• Explore Different Ways to Cope
• Ask for Support
• LiveLoveLaugh

44.
Resources
NCCN Patient Guidelines: http://www.nccn.org/patients/guidelines/ovarian/index.html
NCI Designated Cancer Centers:
http://www.cancer.gov/researchandfunding/extramural/cancercenters
NCI’s Translational Research Program: Ovarian Cancer SPORES
http://trp.cancer.gov/spores/ovarian.htm
Society of Gynecologic Oncology (SGO): Information for patients
https://www.sgo.org/patients-caregivers-survivors/
NOCC: Ovarian Cancer Resource Guide for Women with Recurrent Disease
http://www.ovarian.org/assets/pdf/NOCC_Recurrent.pdf
MSKCC About Herbs
https://www.mskcc.org/cancer-care/treatments/symptom-management/integrative-medicine/herbs
SHARE Clinical Trial Matching Service through EmergingMed
http://www.sharecancersupport.org/share-new/clinicaltrial_1/clinicaltrial/
SHARE: http://www.sharecancersupport.org/share-new/oexplore/
Gilda’s Club NYC: http://gildasclubnyc.org/
CancerCare: http://www.cancercare.org/patients_and_survivors
OCNA—Ovarian Cancer National Alliance: http://www.ovariancancer.org/
NOCC—National Ovarian Cancer Coalition: http://www.ovarian.org/
OCRF—Ovarian Cancer Research Fund: http://www.ocrf.org/
The Human Side of Cancer: Living With Hope, Coping With Uncertainty
by Jimmie Holland, MD (Chapter Two: The Tyranny of Positive Thinking)
Kevin MD Article about Positive Thinking quoting Jimmie Holland:
http://www.kevinmd.com/blog/2011/06/positive-thinking-affects-patients-illnesses.html