The survival rates for all cancers combined and for certain site-specific cancers have improved significantly since the 1970s, due, in part, to both earlier detection and advances in treatment. Survival rates markedly increased for cancers of the prostate, breast, colon, rectum, and for leukemia. With new treatment techniques and increased utilization of screening, there is hope for even greater improvements in the not-too-distant future.
What's New in Ovarian Cancer Treatment
What’s new in Ovarian Cancer Treatment Mildred R. Chernofsky, MD Associate Clinical Professor Department of Obstetrics and Gynecology George Washington University & Uniformed Services UniversitySibley Center for Gynecologic Oncology and Advanced Pelvic Surgery September 13, 2012 1
Epithelial Ovarian CancerSecond 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
5 9•Leading Cause of Gynecologic Cancer Death• More women die of ovarian cancer than cervical and•endometrial cancer combined 3
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
Surgery is first step in treatmentServes 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 treatment09/24/12 5
Following SurgeryChemotherapy for Advanced OvarianCancer• 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 Trial09/24/12 9
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 cancer09/24/12 14
Following SurgeryChemotherapy for Advanced OvarianCancer• 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 Trial09/24/12 15
Angiogenesis= buildingnew blood vessels – Formation of new blood vessels – Healthy versus disease states – Angiogenic switch = VEGF=vascular endothelial growth factor
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 research09/24/12 National Cancer Institute – update 4/2012 17
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
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
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
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 Meeting09/24/12 21
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.
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.
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.
Questions??• Acknowledge & Thank: GynecoLogic Cancer Collaborative: Society of Gynecologic Oncologists (SGO), IMER (Institute for Medical Education and Research): slides Office contact number - 202-243-529509/24/12 25