Sibley Memorial Hospital's Knowledge is Power lecture series on Ovarian Health. Presented by Mildred R. Chernofsky, M.D., on September 13, 2012.

1. What’s new in Ovarian
Cancer Treatment
Mildred R. Chernofsky, MD
Associate Clinical Professor
Department of Obstetrics and Gynecology
George Washington University & Uniformed Services University
Sibley Center for Gynecologic Oncology and Advanced Pelvic Surgery
September 13, 2012
1

2. Epithelial Ovarian Cancer
Second Most Common Gynecologic Cancer
(3% of all cancers diagnosed in women)
• 22,280 new ovarian cancers (2012)
• 15,500 deaths (2012)
2
American Cancer Society, Cancer Facts and Figures 2012

3. 5
9
•Leading Cause of Gynecologic Cancer Death
• More women die of ovarian cancer than cervical and
•endometrial cancer combined 3

4. Epithelial Ovarian Cancer
– It is a more common cancer in older
women than in younger women
(except- inherited)
– At presentation:
• About 75 % will have Advanced
Disease (Stage III/IV)
09/24/12 4

5. Surgery is first step in treatment
Serves 2 purposes:
– If disease is extensive- take out as much
disease as surgically and safely possible:
tumor debulking
– If disease seems limited- tumor staging
allows knowledge about extent of
disease (biopsies are done of lymph
nodes, peritoneum and omentum)
• Prognosis
• Additional treatment
09/24/12 5

6. Tumor Debulking (aka cytoreduction)
09/24/12 6

7. Needs tumor staging biopsies
09/24/12 7

8. 09/24/12 8

9. Following Surgery
Chemotherapy for Advanced Ovarian
Cancer
• intravenous paclitaxel and carboplatin
every 21 days (1996)
• Intravenous (D1)/intraperitoneal
(D8)paclitaxel and intravenous
(D2)cisplatin every 21 days (2006)
• Dose dense weekly paclitaxel and every
21 days carboplatin (2009)
• Clinical Trial
09/24/12 9

10. intraperitoneal
09/24/12
Intravenous 10

11. 09/24/12 11

12. Following Surgery
Chemotherapy for Advanced Ovarian
Cancer
• Dose dense weekly paclitaxel and
every 21 days carboplatin
09/24/12 12

13. 09/24/12 13

14. 3 Year survival
65.1 % 72.1 %
Conclusion: Dose dense weekly paclitaxel plus carboplatin
improved survival compared with the conventional
regimen and represents a new treatment option in women
with advanced epithelial ovarian cancer
09/24/12 14

15. Following Surgery
Chemotherapy for Advanced Ovarian
Cancer
• intravenous paclitaxel and carboplatin
every 21 days (1996)
• Intravenous (D1)/intraperitoneal
(D8)paclitaxel and intravenous
(D2)cisplatin every 21 days (2006)
• Dose dense weekly paclitaxel and every
21 days carboplatin (2009)
• Clinical Trial
09/24/12 15

16. Angiogenesis= building
new blood vessels
– Formation of new blood vessels
– Healthy versus disease states
– Angiogenic switch = VEGF=vascular endothelial growth factor

17. Building of new vessels= angiogenesis
• In some patients with ovarian cancer, adding a drug
that blocks vessel formation (bevacizumab) increases
time to disease progression and may improve
survival**
• Bevacizumab is a targeted therapy (2006-2012, ongoing).
• First targeted therapy in ovarian cancer.
• New agents being developed that similarly block
blood vessel formation at other molecular steps
• Active ongoing research
09/24/12 National Cancer Institute – update 4/2012 17

18. PARP Inhibitors (2010, 2011, 2012- ongoing)
• Cancer cells have mechanisms to repair damaged
DNA.
• PARP proteins help repair DNA.
• DNA damage may be caused by normal cell actions,
UV light, some anticancer drugs, and radiation used
to treat cancer. It may cause cancer cells to die.
• PARP inhibitors= a substance that blocks an enzyme
involved in many functions of the cell, including the
repair of DNA damage.
• It is a type of targeted therapy. Also called poly (ADP-
ribose) polymerase inhibitor.
• Goal of PARP inhibitors -
09/24/12 NCI Dictionary of Cancer Terms-: www.cancer.gov 18

19. PARP Inhibitors and BRCA
• The proteins produced by BRCA1 and BRCA2 are
involved in a different DNA repair mechanism than
that involving PARPs. It was thought, therefore, that
treatment with a PARP inhibitor would further reduce
the ability of cancer cells with BRCA gene mutations
to repair damaged DNA and increase their rate of cell
death, a concept known as synthetic lethality.
• A PARP inhibitor called olaparib (AZD2281) has
already shown promising activity against breast and
ovarian cancers in women with BRCA1 or BRCA2
gene mutations.
Dr. Elise Kohn—
09/24/12 19
http://www.cancer.gov/clinicaltrials/featured/trials/NCI-11-C-0022

20. PARP Inhibitors and BRCA
• Because many chemotherapy drugs work by
damaging DNA, another way to use PARP inhibitors
would be to combine them with DNA-damaging
drugs, such as carboplatin. Increasing the rate of
DNA damage while inhibiting DNA repair should also
reduce cancer cells’ ability to grow and divide,
whether they have BRCA gene mutations or not.
• In preliminary research , combining carboplatin and
the PARP inhibitor olaparib in breast and ovarian
cancer patients with BRCA gene mutations was
shown to be safe and have anticancer activity.
Dr. Elise Kohn—
09/24/12 20
http://www.cancer.gov/clinicaltrials/featured/trials/NCI-11-C-0022

21. PARP Inhibitors
• PARP inhibitors have shown activity in both mutation
carriers for BRCA 1 and 2 and non BRCA patients
with ovarian cancer
• Also activity in platinum sensitive and platinum
resistant patients ovarian cancer patients
• Multiple PARP inhibitors in development/trials
(Olaparib, Veliparib, Rucaparib, BMN 673, others)
• Trials combining PARP inhibitors with chemotherapy.
Dr. Joyce Liu- PARP inhibitors-What’s the truth? 7/26/2012 – GOG Meeting
09/24/12 21

22. Conclusions: Ovarian Cancer
• First line therapy: surgical staging, optimal cytoreduction
(in advanced disease)
• Chemotherapy needs to include taxane and platinum
• IP chemotherapy should be strongly considered.
• There has been an improvement in the survival of
patients with ovarian cancer as a result of better
chemotherapy drugs compared to the 1970’s.

23. Trends in Five-year Relative Survival (%)#
Rates, US, 1975-2005
Site 1975-1977 1984-1986 1999-2005
• All sites 50 54 68*
• Breast (female) 75 79 90*
• Colon 52 59 66*
• Leukemia 35 42 54*
• Lung and bronchus 13 13 16*
• Melanoma 82 87 93*
• Non-Hodgkin lymphoma 48 53 69*
• Ovary 37 40 46*
• Pancreas 3 3 6*
• Rectum 49 57 69*
• Urinary bladder 74 78 82*
* The difference in rates between 1975-1977 and 1999-2005 is statistically significant, (p < 0.05%)
#5-year relative survival rates based on follow up of patients through 2006. Source: Horner et al, SEER Cancer Statistics Review, 1975-2006, NCI, Bethesda,
MD, seer.cancer.gov/csr/1975_2006/,2009.

24. Conclusions: Ovarian Cancer
• First line therapy: surgical staging, optimal cytoreduction (in
advanced disease)
• Chemotherapy needs to include taxane and platinum
• IP chemotherapy should be strongly considered.
• There has been an improvement in the survival of patients
with ovarian cancer as a result of better chemotherapy drugs
compared to the 1970’s.
• Ovarian cancer is still a very lethal disease.
• More research is needed with new promising agents, like
Bevacizumab, PARP inhibitors and other targeted agents,
which may hold the key to further improvement in survival.
• Strongly consider participation in clinical trials- always
something new being looked at to try and further improve
outcomes in ovarian cancer patients.

25. Questions??
• Acknowledge & Thank: GynecoLogic Cancer Collaborative:
Society of Gynecologic Oncologists (SGO), IMER (Institute for
Medical Education and Research): slides
Office contact number - 202-243-5295
09/24/12 25