Osu 2014 asco review salani pres gyn onc
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Ohio State's 2014 ASCO Review Gynecologic Oncology Update Presentation by Dr. Ritu Salani

Ohio State's 2014 ASCO Review Gynecologic Oncology Update Presentation by Dr. Ritu Salani

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Osu 2014 asco review salani pres gyn onc Presentation Transcript

  • 1. Best of ASCO 2014 Gynecologic Oncology Ritu Salani, M.D., M.B.A Associate Professor Division of Gynecologic Oncology Department of Obstetrics & Gynecology The James Cancer Center
  • 2. Objectives • Review studies in recurrent ovarian cancer – Platinum sensitive – Platinum resistant – Additional studies • Discuss the developing role of metformin in endometrial cancer • Provide an update on cervical cancer screening with HPV testing
  • 3. Gynecologic Cancer Cases American Cancer Society. Cancer Facts & Figures. 2008. Atlanta: American Cancer Society; 2008. Estimated cases per year Estimated deaths per year
  • 4. Ovarian cancer • 21,980 cases and 14,270 deaths in 2014 • First line response rates: ~75-80% • Recurrence rate: 60% overall • Defined by the time between primary treatment and detection of relapse – Platinum sensitive: ≥6 months – Platinum resistant : <6 months – Platinum refractory: Progression on therapy
  • 5. Randomized Phase II • Cediranib – Oral tyrosine kinase inhibitor of VEGFR – Toxicities: fatigue, hypertension, diarrhea – Phase II trials in recurrent ovarian cancer • Overall response rate 17% • PFS 5.2 months • Olaparib – Oral PARP inhibitor – Toxicities: fatigue, myelosuppression, anemia – Phase II trials • Overall response rate 24- 40% • PFS 7-9 months • Synergistic activity • Phase I study demonstrated response rate of 44%
  • 6. Study design • Phase 2 open-label randomized study • Platinum sensitive recurrent ovarian cancer • 1:1 randomization Cediranib 30 mg daily and Olaparib 200 mg BID Olaparib 400 mg BID Disease progression by RECIST v1.1 criteria
  • 7. Progression free survival
  • 8. PFS based on BRCA mutation status
  • 9. Overall response rate
  • 10. PARP inhibition: Next steps • Primary setting in combination with bevacizumab and cytotoxic therapy • Recurrent platinum sensitive disease – BRCA positive – BRCA negative or unknown • Maintenance setting • Combination with targeted agents
  • 11. Platinum Resistant Ovarian Cancer • Pazopanib is a tyrosine kinase inhibitor – Targets VEGFR, PDGFR, and ckit – Demonstrated activity in maintenance setting
  • 12. Study design
  • 13. Survival outcomes
  • 14. Platinum resistant ovarian cancer
  • 15. Study design
  • 16. Progression free survival
  • 17. PM01183 Results • Overall response rate (p=0.006) • Response rate 30% in platinum resistant group
  • 18. Study Study group Arms Outcomes Conclusion OVA-301 Platinum resistant ovarian cancer PLD + Trabectedin versus PLD -OS 22.2 months vs 15.1 months Promising activity PD1 (Nivolumab) Platinum resistant ovarian cancer Nivolumab Response rates of 17% Further studies JGOG 3017 First line therapy for clear cell cancer Carboplatin/ Paclitaxel versus Irinotecan/Ci splatin 2 year PFS and OS similar Need for new treatments CAN-003 Stage III/IV in complete remission CVAC versus observation Improved PFS in second remission Promising activity
  • 19. Molecular biomarkers • Samples from ICON 7 trial • TCGA subclasses: – Immunoreactive – Differentiated – Proliferative – Mesenchymal
  • 20. Survival based on TCGA subclasses
  • 21. Subtype analysis
  • 22. Uterine cancer • 52,630 cases and 8590 deaths in 2014
  • 23. Results • Short exposure of metformin – Reduction of 83% in MAPK and 90% in Phospho- AKT • Current studies – GOG 286 B: recurrent/advanced endometrial cancer with carboplatin/paclitaxel +/- metformin – Phase II studies with everolimus, letrozole, metformin in advanced/recurrent endometrial cancer
  • 24. Cervical cancer • 12,360 cases and 4,020 deaths in 2014
  • 25. Cervical cancer screening • Pap smear/test – Introduced 1941 – ~65 million Pap tests/year – 3.5 million abnormal Pap tests • Human Papillomavirus (HPV) – Discovered in 1956; Cancer link in 1984 – HPV test approved by FDA in 2003
  • 26. ATHENA trial • Designed to evaluate the clinical utility of HPV testing compared to cytology • All women had baseline HPV testing and cytology • At the 3-year visit, all women underwent repeat evaluation.
  • 27. ATHENA trial • 3-year follow-up data from the ATHENA trial indicate that hrHPV primary screening with triage to colposcopy based on genotyping and reflex cytology provides a more sensitive cervical screening strategy than cytology and is more efficient than cotesting. • HPV may be used as primary screening alone!
  • 28. Summary • Ovarian cancer – Promising agents in platinum resistant disease – Further study using PARP inhibition – Understanding of the role of molecular biomarkers and personalized therapy • Endometrial cancer – Supplementation of therapy with metformin – Education on lifestyle behaviors • Cervical cancer – Improved screening tests – Access to care and HPV vaccine need to be highlighted
  • 29. Thank you Ritu.Salani@osumc.edu