Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Ovarian Cancer: What's New?

13,535 views

Published on

Dr. Stephanie Blank and Dr. Melissa Frey update us on the latest developments in ovarian cancer research and treatment from the annual conference of the Society of Gynecologic Oncology. Dr. Blank is a gynecologic oncologist at Perlmutter Cancer Center at NYU Langone Medical Center and an associate professor at NYU School of Medicine. Dr. Frey is a Gynecological Oncology Fellow at NYU Langone Medical Center.

Published in: Health & Medicine
  • Don't even THINK about buying any uterine fibroids product, drugs or going on a gimmick fibroids program until you read my revealing, no-holds barred holistic uterine fibroids cure book. ➤➤ http://ishbv.com/fibroids7/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Be the first to like this

Ovarian Cancer: What's New?

  1. 1. Ovarian Cancers: Evolving Paradigms in Research and Care Report Release Wednesday, March 2, 2016
  2. 2. • Congressionally mandated report • Sponsored by the Centers for Disease Control and Prevention • IOM charged with completing the work • Multidisciplinary committee assembled • Four in-person meetings Background
  3. 3. Statement of Task An ad hoc committee under the auspices of the Institute of Medicine will review the state of the science in ovarian cancer and formulate recommendations for action to advance the field. The committee will: • Summarize and examine the state of the science in ovarian cancer research, • Identify key gaps in the evidence base and the challenges to addressing those gaps, continued
  4. 4. Statement of Task (continued) • Consider opportunities for advancing ovarian cancer research, and • Examine avenues for translation and dissemination of new findings and communication of new information to patients and others. The committee will make recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of and morbidity and mortality from ovarian cancer.
  5. 5. Biology Innovative Research Designs Supportive Care Research & Practice Prevention & Early Detection Diagnosis & Treatment Secondary Prevention & Monitoring for Recurrence Management of Recurrent Disease End-of-Life Care Long-Term Survivorship Methods to Reduce Practice- Related Disparities Intervention Development Previvorship Survivorship Conceptual Model
  6. 6. 1. Prioritize study of high-grade serous carcinoma 2. More subtype-specific research is needed to define various subtype characteristics 3. Collaboration is essential a. Pooling and sharing of data and biospecimens b. Use of consortia 4. Dissemination and implementation are final steps for knowledge translation Overarching Concepts
  7. 7. Ovarian Cancers: Evolving Paradigms in Research and Care #Ovarian Cancers www.nas.edu/OvarianCancers
  8. 8. High-grade serous carcinoma Carcinosarcoma Endometrioid carcinoma 70% - 74% 7% - 24% 10% - 26% 2% - 6% 0.6% - 7.1% 3% - 5% 1% - 7% Ovarian Carcinomas – Not one disease
  9. 9. Ovarian Carcinomas – Origins
  10. 10. The fallopian tube is a likely site of most HGSC and genetic models are expanding
  11. 11. Recommendation • Strategies to increase genetic counseling and testing for all women with ovarian cancer • Wider offering of cascade testing • Determine analytic performance and clinical utility of testing for germline mutations beyond BRCA1 and BRCA2 and mismatch repair genes associated with Lynch Syndrome.
  12. 12. Supportive Care Along the Survivorship Trajectory
  13. 13. • Most research focuses on treatment rather than on how to improve the management of the acute and long-term physical and psychosocial effects of diagnosis and treatment across the trajectory of survivorship. • Most research on survivorship aggregates patients of all cancer types • Survivorship research on ovarian cancer rarely distinguishes different subgroups – age, racial and ethnic groups, stage, histology, etc. Key Findings in IOM Report
  14. 14. Dissemination & Implementation of Knowledge “an active approach of spreading evidence-based interventions to the target audience via determined channels using planned strategies”
  15. 15. Biology Innovative Research Designs Supportive Care Research & Practice Prevention & Early Detection Diagnosis & Treatment Secondary Prevention & Monitoring for Recurrence Management of Recurrent Disease End-of-Life Care Long-Term Survivorship Intervention Development Previvorship Survivorship Prevention & Early Detection Diagnosi s & Treatmen t Secondary Prevention & Monitoring for Recurrence Previvorshi p Survivorship Managemen t of Recurrent Disease End-of-Life Care Long-Term Survivorship Methods to Reduce Practice-Related Disparities Methods to Reduce Practice-Related DisparitiesSupportive Care Research & Practice Final steps for knowledge translation into practice for all stakeholders
  16. 16. • Current methods for early detection in the general or high-risk population do not have substantial impact on mortality. • Proven preventive strategies exist. • All women with invasive ovarian cancer should receive germline genetic testing. • Genetic counseling and testing for the first-degree relatives of women with a hereditary cancer syndrome or germline mutation. • Uniform implementation of the standard of care and the inclusion of supportive care across the survivorship trajectory. Some key messages
  17. 17. Survivors’ acceptance of treatment side effects evolves as goals of care change over the cancer continuum Melissa K. Frey New York University Langone Medical Center
  18. 18. Verbal Disclosure • Nothing to disclose.
  19. 19. • Ovarian cancer disease course – Long overall survival – Multiple treatment regimens • What are meaningful clinical trial endpoints? – Overall survival – Progression-free survival – Patient reported outcomes – Health-related quality of life • FDA workshop on alternative clinical trial endpoints (September 3, 2015) – Co-sponsored by: • Society of Gynecologic Oncology (SGO) • American Society of Clinical Oncology (ASCO) • American Association for Cancer Research (AACR) Herzog TJ et al. Gynecol Oncol. 2014. Background
  20. 20. • Exploring patient preferences – OCNA Clinical Trial Endpoints: What do our patients consider important (2013) – NYU/SHARE: A qualitative study of ovarian cancer survivors' perceptions of endpoints and goals of care (2014) • Shared decision-making – Physician awareness of patient goals – Incorporating goals when selecting treatment – Maximizing treatment efficacy AND quality of life Minion LE et al. Gynecol Oncol. 2016. Frey MK et al. Gynecol Oncol. 2014. Background
  21. 21. To determine whether survivors’ acceptance of treatment side effects changes over the disease continuum. Objective
  22. 22. • Ovarian Cancer Survivorship Questionnaire – Developed by Annie Ellis – Combination of OCNA Clinical Trial Endpoints and NYU/SHARE – 30 questions, Likert-type scale and multiple choice • Questionnaire available online (8/1/2015-8/12/2015) – Survivor networks – Social media • Completed online by self-identified ovarian cancer survivors • Consent for participation provided electronically • Exempt status from NYU Langone Medical Center Institutional Review Board Annie Ellis Patient Advocate Methods
  23. 23. Age (years) (N = 328) 18-35 7 (2%) 36-50 63 (19%) 51-60 142 (43%) 61-70 91 (28%) >70 25 (8%) Race / Ethnicity Non-Hispanic white 303 (92%) Hispanic 10 (3%) Non-Hispanic black 5 (2%) Asian/Pacific Islander 3 (1%) Other or Unknown 7 (2%) Disease site Ovary 267 (81%) Fallopian tube 21 (6%) Primary peritoneal 37 (11%) Unknown 3 (1%) Disease stage I 55 (17%) II 33 (10%) III 194 (59%) IV 37 (11%) Unknown 9 (3%) Results - Demographics
  24. 24. Time since cancer diagnosis (N = 328) <12 months 44 (13%) 1-4 years 184 (56%) 5-9 years 59 (18%) 10-14 years 23 (7%) 15-19 years 10 (3%) > 20 years 7 (2%) Recurrent disease Yes 142 (43%) No 180 (55%) No answer 6 (2%) Undergoing treatment at time of questionnaire completion Yes 119 (36%) No 205 (63%) No answer 4 (1%) Results – Demographics 0 20 40 60 80 100 0 1 2 3 4 > 5 #Participants # Prior treatment regimens received Prior treatment regimens
  25. 25. What is your treatment goal? Overall survival 45% Progression-free survival 12% Quality of life 41% No answer 2%
  26. 26. What is most meaningful to you? Overall survival 39% Minimizing treatment side effects 11% Minimizing disease symptoms 6% Ability to engage in daily activities 35% Attend a life event 0% Time off treatment 6% Other 3%
  27. 27. When selecting a treatment, what is your expectation? Cure 35% Remission 49% Stable disease 16% All participants
  28. 28. When selecting a treatment, what is your expectation? P < 0.001 Cure 50% Remission 45% Stable disease 5% Participants without recurrence (N = 180) Cure 16% Remission 53% Stable disease 31% Participants with at least one recurrence (N = 142)
  29. 29. Which of these treatment side effects would you tolerate? Goal of treatment: Cure Remission Stable disease Cure Remission Stable disease Bowel obstruction Shortness of breath Infection Mucositis Ototoxicity Hand-foot syndrome Pain Memory loss Nausea/vomiting Headache Sexual side effects Flu-like symptoms Arthralgia Skin changes Neuropathy Constipation Diarrhea Fatigue Alopecia
  30. 30. Treatment side effects (Goal = Cure) % Participants willing to accept the side effect 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Bowel obstruction Shortness of breath Infection Mucositis Ototoxicity Hand-foot syndrome Pain Memory loss Nausea/vomiting Headache Sexual side effects Flu-like symptoms Arthralgia Skin changes Neuropathy Constipation Diarrhea Fatigue Alopecia
  31. 31. Percentage of survivors who would accept treatment side effects based on the goal of treatment (Goal = Cure) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
  32. 32. Percentage of survivors who would accept treatment side effects based on the goal of treatment (Cure vs. Remission) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
  33. 33. Percentage of survivors who would accept treatment side effects based on the goal of treatment (Cure vs. Remission vs. Stable disease) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
  34. 34. Expectation of cure among survivors with recurrent disease Cure 16% Remission 53% Stable disease 31% Participants with recurrent disease (N=142, 43%)
  35. 35. Expectation of cure among survivors with recurrent disease Participants with recurrent disease (N=142, 43%) Stable disease Cure (22 participants) Remission 0% 20% 40% 60% 80% 100% Bowel obstruction Shortness of breath Infection Mucositis Ototoxicity Hand-foot syndrome Pain Memory loss Nausea/vomiting Headache Sexual side effects Flu-like symptoms Arthralgia Skin changes Neuropathy Constipation Diarrhea Alopecia Fatigue
  36. 36. Cure Remission Stable disease I would accept any side effects for a CURE!! I’d take anything that has less than 20% chance of killing me immediately. I would tolerate these side effects if they were temporary. I'd rather not tolerate any side effects. None! Depends on severity and quality of life tradeoffs. This is a much bigger issue if ‘stable disease’is the best you can get. Facing this now, I have learned that my tolerance for side effects is pretty low under these conditions. Survivor comments by goal of treatment
  37. 37. • Acceptance of treatment side effects declines with changing goals – Cure  remission  stable disease • Goal of cure drives willing acceptance of treatment toxicity • When selecting treatment balance treatment toxicities and quality of life measures • Survivors’ decision tool for selecting treatment therapies for recurrent disease in development Conclusions
  38. 38. Co-authors • Annie E. Ellis, Patient Advocate • Laura Koontz, PhD • Savannah Shyne, MPH • Jing-Yi Chern, MD • Jessica Lee, MD • Stephanie V. Blank, MD Acknowledgements
  39. 39. Higher rates of clinically actionable multigene panel results in Ashkenazi Jewish patients Melissa Frey New York University Langone Medical Center
  40. 40. Verbal disclosure • Nothing to disclose.
  41. 41. • Next-generation sequencing – Rapid – Cost-effective – Virtually unlimited number of genes – Ovarian cancer genes – BRCA1, BRCA2, BARD1, BRIP1, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D • Clinical actionability – Actionable mutations • Mutations with known clinical manifestations and well-outlined cancer screening guidelines – Non-actionable mutations • Mutations in low- to moderate-risk genes for which consensus management guidelines have not been established Norquist BM et al. JAMA Oncol. 2015 Multigene panel testing for cancer syndromes
  42. 42. To determine if there are specific patient populations in which multigene panels would be more likely to affect clinical management. Objective
  43. 43. • Review of multigene panel testing results at a single institution • Study period: June 2013 - January 2015 • All genetic testing performed after consultation by a certified genetic counselor • Mutations were characterized as actionable or non-actionable – National Comprehensive Cancer Network (NCCN) guidelines – Genes not addressed by NCCN guidelines – Consensus statements – Expert opinion • Statistical methods: T-test, Chi-square, Fisher’s exact test Methods
  44. 44. Results - Patient Demographics Gender (N = 454) Female 435 (96%) Male 19 (4%) Race/ethnicity Non-Hispanic white 362 (80%) Non-Hispanic black 31 (7%) Hispanic 29 (6%) Asian/Pacific Islander 32 (7%) Ashkenazi Jewish ancestry Ashkenazi Jewish 138 (30%) Non-Ashkenazi Jewish 316 (70%) Personal history of cancer 354 (78%) Breast 251 (55%) Ovarian 49 (11%) Uterine 26 (6%) Colorectal 20 (4%) Family history of cancer 417 (92%)
  45. 45. Results - Multigene panels 454 patients Pathogenic mutations 62 mutations identified 56 patients (12%) 19 genes VUS 291 VUS identified 196 patients (43%) 38 genes Actionable mutations APC, ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MEN1, MLH1, MSH6, PALB2, PMS2, PTEN, RAD51D Non-actionable mutations CDKN2A, FAM175A, FANCC, FLCN, MUTYH
  46. 46. Actionable 79% Non- actionable 21% • Actionable mutations – 10% of all patients (47/454) – 79% of all mutations (49/62) • Non-actionable mutations – 2% of all patients (9/454) – 21% of all mutations (13/62) • Age, gender, race, ethnicity, personal history of cancer and family history of cancer were NOT associated with finding an actionable mutation Results – Clinical Actionability Mutations (N = 62)
  47. 47. • No differences when comparing Ashkenazi to non-Ashkenazi patients: – Gender, personal history of cancer, family history of cancer, # mutations, # VUS • Mutations in Ashkenazi patients were significantly more likely to be clinically actionable Results - Ashkenazi Jewish ancestry Ashkenazi Jewish (N=20) Non-Ashkenazi Jewish (N=42) P value Actionable mutations (N = 49) 19 (95%) 30 (71%) Non-actionable mutations (N = 13) 1 (5%) 12 (29%) 0.04
  48. 48. Ashkenazi Jewish (N=138) Actionable mutation Non-actionable mutation Pathogenic mutations in Ashkenazi and non-Ashkenazi Patients Non-Ashkenazi Jewish (N=316) FANCC, 1 APC, 6 BARD1, 1 BRCA2, 1 BRCA1, 1 BRIP1, 1 CHEK2, 7 MLH1, 1 MSH6, 1 CDKN2A, 1 FAM175A, 1 FANCC, 2 FLCN, 1 MUTYH, 7 ATM, 3 BRCA2, 4 BRCA1, 2 BRIP1, 5 CHEK2, 6 MEN1, 1 MLH1, 2 PALB2, 2 PMS2, 1 PTEN, 3 RAD51D, 1
  49. 49. Ashkenazi Jewish (N=138) Actionable mutation Non-actionable mutation Pathogenic mutations in Ashkenazi and non-Ashkenazi Patients Non-Ashkenazi Jewish (N=316) FANCC, 1 APC, 6 BARD1, 1 BRCA2, 1 BRCA1, 1 BRIP1, 1 CHEK2, 7 MLH1, 1 MSH6, 1 CDKN2A, 1 FAM175A, 1 FANCC, 2 FLCN, 1 MUTYH, 7 ATM, 3 BRCA2, 4 BRCA1, 2 BRIP1, 5 CHEK2, 6 MEN1, 1 MLH1, 2 PALB2, 2 PMS2, 1 PTEN, 3 RAD51D, 1 2 BRCA1/2 mutations BRCA1 (1) BRCA2 (1) 6 BRCA1/2 mutations BRCA1 (2) BRCA2 (4)
  50. 50. FANCC, 1 APC, 6 BARD1, 1 BRCA2, 4 BRCA1, 4BRIP1, 1 CHEK2, 7 MLH1, 1 MSH6, 1 Ashkenazi Jewish (N=183) Actionable mutation Non-actionable mutation Non-Ashkenazi Jewish (N=374) CDKN2A, 1 FAM175A, 1 FANCC, 2 FLCN, 1 MUTYH, 7 ATM, 3 BRCA2, 4 BRCA1, 2BRIP1, 5 CHEK2, 6 MEN1, 1 MLH1, 2 PALB2, 2 PMS2, 1 PTEN, 3 RAD51D, 1 8 BRCA1/2 mutations BRCA1 (4) BRCA2 (4) 6 BRCA1/2 mutations BRCA1 (2) BRCA2 (4) BRCA1/2 mutations from multigene panels and targeted single gene BRCA1/2 screening (N=557)
  51. 51. Ashkenazi Jewish (N=138) Actionable mutation Non-actionable mutation Pathogenic mutations in Ashkenazi and non-Ashkenazi Patients Non-Ashkenazi Jewish (N=316) FANCC, 1 APC, 6 BARD1, 1 BRCA2, 1 BRCA1, 1 BRIP1, 1 CHEK2, 7 MLH1, 1 MSH6, 1 CDKN2A, 1 FAM175A, 1 FANCC, 2 FLCN, 1 MUTYH, 7 ATM, 3 BRCA2, 4 BRCA1, 2 BRIP1, 5 CHEK2, 6 MEN1, 1 MLH1, 2 PALB2, 2 PMS2, 1 PTEN, 3 RAD51D, 1 Evolving understanding of actionable vs. non-actionable
  52. 52. • Multigene panel testing discovered: • Mutations in 56 patients (12%) • VUS in 196 patients (43%) • Multigene panel testing should be considered in Ashkenazi Jewish patients • Majority of mutations are actionable (95%) • Mutations occur in multiple genes and are not limited to BRCA1/2 Conclusions
  53. 53. Co-authors • Gabriella Sandler, BS • Rachel Sobolev, BS • Sarah Kim, MD • Rachelle Chambers, MS, CGC • Jessica Martineau, MS, CGC • Rebecca Y. Bassett, MS, CGC • Stephanie V. Blank, MD Acknowledgments
  54. 54. Gene Recommendations Source APC Actionable Colorectal cancer - Colonoscopy every 5 years starting at age 40 Expert opinion ATM Actionable Breast cancer - Recommend breast MRI NCCN Guidelines BARD1 Emerging evidence suggesting actionability Ovarian cancer - Consider risk-reducing salpingo-oophorectomy Norquist et al. JAMA Oncol . 2015. Ovarian cancer - Recommend/consider risk-reducing salpingo-oophorectomy Breast cancer - Recommend breast MRI, discuss option of risk-reducing mastectomy Ovarian cancer - Recommend/consider risk-reducing salpingo-oophorectomy Breast cancer - Recommend breast MRI, discuss option of risk-reducing mastectomy BRIP1 Actionable Ovarian cancer - Risk-reducing salpingo-oophorectomy NCCN Guidelines CHEK2 Actionable Breast cancer - Recommend breast MRI NCCN Guidelines Parathyroid glands, anterior pituitary, enteropancreatic endocrine cell tumors Biochemical tests – calcium, PTH, gastrin, gastric acid output, secretin-stimulated gastrin, fasting glucose, insulin, PRL, IGF-1 Imaging tests – MRI/CT scan Colorectal cancer - Colonoscopy Endometrial and ovarian cancer - Consider option of risk-reducing hysterectomy and bilateral salpingo-oophorectomy, annual office endometrial sampling is an option Gastric and small bowel cancer - Selected individuals or families or those of Asian descent may consider EGD with extended duodenoscopy Urothelial cancer - Consider annual urinalysis Colorectal cancer - Colonoscopy Endometrial and ovarian cancer - Consider option of risk-reducing hysterectomy and bilateral salpingo-oophorectomy, annual office endometrial sampling is an option PALB2 Actionable Breast cancer - Recommend breast MRI, discuss option of risk-reducing mastectomy NCCN Guidelines Colorectal cancer - Colonoscopy Endometrial and ovarian cancer - Consider option of risk-reducing hysterectomy and bilateral salpingo-oophorectomy, annual office endometrial sampling is an option Endometrial cancer - Discuss option of risk-reducing hysterectomy, consider annual random endometrial biopsies and/or ultrasound Breast cancer - Recommend breast MRI, discuss option of risk-reducing mastectomy Thyroid cancer - Annual thyroid ultrasound Colorectal cancer - Colonoscopy Renal cancer - Consider renal ultrasound RAD51D Actionable Ovarian cancer - Recommend/consider risk-reducing salpingo-oophorectomy NCCN Guidelines Actionable Mutations PMS2 Actionable NCCN Guidelines PTEN Actionable NCCN Guidelines MSH6 Actionable NCCN Guidelines MLH1 Actionable NCCN Guidelines MEN1 Actionable Expert opinion / consensus statements BRCA1 Actionable NCCN Guidelines BRCA2 Actionable NCCN Guidelines CDKN2A Non-actionable FAM175A Non-actionable FANCC Non-actionable FLCN Non-actionable MUTYH Non-actionable Non-Actionable Mutations
  55. 55. A PHASE III CLINICAL TRIAL OF BEVACIZUMAB WITH IV VERSUS IP CHEMOTHERAPY IN OVARIAN, FALLOPIAN TUBEAND PRIMARY PERITONEAL CARCINOMA NCI-SUPPLIED AGENT(S): BEVACIZUMAB (NSC #704865, IND #7921) NCT01167712 a GOG/NRG Trial (GOG 252) Joan L. Walker; Mark F Brady; Paul A DiSilvestro; Keiichi Fujiwara; David Alberts; Wenxin Zheng; Krishnansu Tewari; David E Cohn; Matthew Powell; Linda van Le; Stephen Rubin; Susan A Davidson; Heidi J Gray; Steven Waggoner; Tashanna Myers; Carol Aghajanian; Angeles Alvarez Secord; Robert S Mannel
  56. 56. GOG 252: IP chemo and dose dense Paclitaxel showed improved OS, both have toxicities; which is best? Should we use dose dense Paclitaxel? Should we use IP chemotherapy? Should we use Bevacizumab? • JGOG 3016 showed improved OS, but not replicated in the US • GOG 172 showed survival advantage, but was toxic, with only 42% receiving 6 cycles; additional studies were done to address the toxicity: -GOG9916/17 Substituted IP carbo for cisplatin -GOG9921 Reduced IP cisplatin dose • GOG 218 showed improved PFS with Bev, and feasibly safe with IP Chemo Arm 1: Dose dense Paclitaxel Arm 2: IP Chemo substitute Arm 3: Include Bevacizumab Key questions for GOG 252 Indications and contemporary results Implications for GOG 252 schema All: IP chemo, reduced cisplatin dose
  57. 57. Arm 1 Arm 2 Arm 3 GOG 252: Schema • Stage II-III Epithelial Carcinoma: Ovary, Fallopian Tube, Peritoneal • Resected to optimal: less than or equal to 1 cm visible tumor by surgeon report • Exploratory: suboptimal (7%) and Stage IV (5%) Eligibility
  58. 58. Differences in Dosing in GOG 252 Arm 3 IP Cisplatin compared to GOG 172 • Dose reduction cisplatin(100 down to 75 mg/m2) • Infusion time reduction 135 mg/m2 paclitaxel(3 hr instead of 24h) • All outpatient therapy • Bevacizumab 15 mg/m2 for all arms on cycles 2-22 • Comparison arm dose dense paclitaxel with carbo IV AUC 6- GOG 262 (JGOG) • Second experimentalArm IP carbo and dose dense paclitaxel
  59. 59. Progression Free Survival Optimal Stage II-III (10% stage II) • Estimated hazard ratios, and logrank tests are adjusted for stage of disease and size of residual disease micro vs < 1cm • CT required every 6 months for surveillance (not required in GOG 114/172) Arm N Events Median PFS HR [95% CI] Logrank Logrank IV Carbo 461 303 26.8 months Reference arm P-value Chi square IP Carbo 464 300 28.7 months 0.947 [0.808- 1.11] 0.416 0.661 IP Cisp 456 307 27.8 months 1.01 [0.858-1.18] 0.727 0.122
  60. 60. P r o g r e s s i o n - F r e e S u r v iv a l b y T r e a t m e n t G r o u p S ta g e II o r III O p ti m a l l y D e b u l k e d T r e a tm e n t G r o u p E ve n ts T o ta l M e d i a n ( m o s ) 1 : C r b ( IV ) + T + B e v 3 0 3 4 6 1 2 6 .8 2 : C r b ( IP ) + T + B e v 3 0 0 4 6 4 2 8 .7 3 : C i s ( IP ) + T + B e v 3 0 7 4 5 6 2 7 .8 0 .2 0 .4 0 .6 0 .8 1 .0 ProportionSurviving Progression-Free 3 : C i s ( IP ) + T + B e v 2 : C r b ( IP ) + T + B e v 1 : C r b ( IV ) + T + B e v T r e a tm e n t G r o u p 2 6 .8 2 8 .7 2 7 .8 E ve n ts T o ta l M e d i a n ( m o s ) 3 0 3 4 6 1 3 0 0 4 6 4 3 0 7 4 5 6 Progression Free Survival Optimal Stage II-III 0.0 0 12 24 36 48 60 72 Months on Study 1 461 387 244 169 111 37 0 2 464 391 262 177 125 39 0 3 456 372 255 168 120 34 0
  61. 61. P r o g r e s s i o n -F r e e S u r v iv a l b y T r e a tm e n t G r o u p S ta g e III w i th N o G ro s s R e s i d u a l D i s e a s e • T re a tm e n t G ro u p E ve n ts To ta l M e d i a n ( m o s ) 1 : C rb (IV )+ T + B e v 1 4 4 2 3 9 3 1 .3 • 2 : C rb (IP )+ T + B e v 1 4 5 2 3 8 3 1 .8 • 3 : C i s (IP )+ T + B e v 1 3 8 2 3 9 3 3 .8 0 .2 0 .4 0 .6 0 .8 1 .0 ProportionSurviving Progression-Free 3 : C i s (IP )+ T + B e v 2 : C rb (IP )+ T + B e v 1 : C rb (IV )+ T + B e v T re a tm e n t G ro u p 3 1 .3 3 1 .8 3 3 .8 1 4 4 2 3 9 1 4 5 2 3 8 1 3 8 2 3 9 E ve n ts T o ta l M e d i a n ( m o s ) Progression Free Survival Optimal Stage III NGR 0.0 0 12 24 36 48 60 72 Months on Study 1 239 203 141 97 66 21 0 2 238 209 152 103 72 21 0 3 239 204 150 104 76 24 0
  62. 62. Across Study Comparisons for PFS Arm Study PFS Median in mos No visible dx Stage 3 PFS median mos 1 cm or less visible dx GOG 114 & 172 IV cisplatin 33.4 GOG 172 IV cisplatin 43.2 18.3 GOG 252 IV carbo 31.3 26.8 (10% stage II) GOG 114 & 172 IP cisplatin 43.2 GOG 172 IP cisplatin 60.4 23.8 GOG 252 IP carboplatin 31.8 28.7 (10% Stage II) GOG 252 IP cisplatin 33.8 27.8 (10% Stage II)
  63. 63. Discussion • Survival for optimal and no residual disease participants will not be available for a few years. • Dose reductions of paclitaxel and cisplatin as well as cross- over may have compromised efficacy. • Dose dense paclitaxel may have improved efficacy to allow us to abandon IP chemo- must we wait- combine both? • Bevacizumab interactions could have clouded analysis
  64. 64. Conclusions • All arms have excessive toxicity • Neurotoxicity is similarly high in all arms • Reserve changes in treatment recommendations until survival data available for no residual disease high grade serous Stage III participants. • IP Cisplatin increases bevacizumab associated HTN

×