1 / 17

GOG0172: The Dings

GOG0172: The Dings. The recommended regimen is not feasible Substitution of carboplatin for cisplatin Reduce cisplatin from 100 mg/m 2 to 75 mg/m 2 Change paclitaxel infusion and/or schedule Need for 6 cycles not established Role of intraperitoneal delivery not established

amalie
Download Presentation

GOG0172: The Dings

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. GOG0172: The Dings • The recommended regimen is not feasible • Substitution of carboplatin for cisplatin • Reduce cisplatin from 100 mg/m2 to 75 mg/m2 • Change paclitaxel infusion and/or schedule • Need for 6 cycles not established • Role of intraperitoneal delivery not established • Trial design flawed (too many variables) • Dose-intensity hypothesis not validated • Potential role of biology, angiogenesis, microenvironment • This should not be our research priority

  2. GOG157: Ovarian (adjuvant) • Epithelial Ovarian Cancer • Stage IC/II any grade • Stage IA/B high grade • No prior therapy Paclitaxel 175 mg/m2 (3 h) Carboplatin AUC=7.5 I x 3 Paclitaxel 175 mg/m2 (3 h) Carboplatin AUC=7.5 II x 6 • Only 70% met eligibility criteria (133 excluded) • 107/457 (23%) were incompletely staged • Hematologic toxicity and neuropathy increased with 6 cycles Open: 20-Mar-95 Closed: 25-May-98 Accrual: 457 pts Bell JG, et al. Gynecol Oncol 102:432-9, 2006

  3. GOG157: Ovarian (adjuvant) Carbo-Paclitaxel (x6) (n = 214) 83% @ 5 y Carbo-Paclitaxel (x3) (n = 213) 81% @ 5 y Hazard Ratio = 1.02 95% CI = 0.662 – 1.57, p=0.94 (includes 107 surgical exclusions) Bell JG, et al. Gynecol Oncol 102:432-9, 2006

  4. GOG111: Ovarian (suboptimal III/IV) Cisplatin 75 mg/m2 Cyclophosphamide 650 mg/m2 I • Epithelial Ovarian Cancer • Suboptimal Stage III/IV • No prior therapy Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) II Open: 13-Apr-90 Closed: 02-Mar-92 Accrual: 410 pts McGuire, et al. N Engl J Med 334:1-6, 1996

  5. GOG132: Ovarian (suboptimal III/IV) I Cisplatin 100 mg/m2 • Epithelial Ovarian Cancer • Suboptimal Stage III/IV • No prior therapy • Crossover allowed II Paclitaxel 200 mg/m2 (24 h) Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) III Open: 20-Mar-92 Closed: 09-May-94 Accrual: 648 pts Muggia, et al. J Clin Oncol 18:106, 2000

  6. 10 m GOG111 & 132: Ovarian (subopt III/IV) GOG-111 (n = 184) CDDP 75 and Paclitaxel 135 Median = 37 m GOG-132 (n = 201) CDDP 75 and Paclitaxel 135 Median = 27 m Muggia, et al. J Clin Oncol 18:106, 2000 McGuire, et al. N Engl J Med 334:1-6, 1996

  7. GOG158: Ovarian (optimal III) Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) I • Epithelial Ovarian Cancer • Optimal Stage III • No prior therapy • Elective Second-Look • Non-Inferiority Design Carboplatin AUC 7.5 Paclitaxel 175 mg/m2 (3 h) II Open: 03-Apr-95 Closed: 26-Jan-98 Accrual: 792 pts (evaluable) Ozols, et al. Proc J Clin Oncol 21:3194, 2003

  8. GOG172: Ovarian (optimal III) • Epithelial Ovarian Cancer • Optimal Stage III • No prior therapy • Elective Second-Look Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) I Cisplatin 100 mg/m2 IP d1 Paclitaxel 135 mg/m2 (24 h) IV d1 Paclitaxel 60 mg/m2 IP d8 II Open: 23-Mar-98 Closed: 29-Jan-01 Accrual: 416 pts (evaluable) Armstrong, et al. NEJM 354:34-43, 2006

  9. CDDP (IV) Paclitaxel (IV) (n = 400) Ozols, et al. J Clin Oncol 21:3194, 2003 GOG172 & 158: Exploratory Analysis CDDP (IP) Paclitaxel (IP+IV) (n = 206) CDDP (IV) Paclitaxel (IV) (n = 210) Armstrong, et al. NEJM 354:34-43, 2006

  10. GOG: Combined Exploratory Analysis GOG172 to GOG158: HR = 0.81 (95% CI 0.59 – 1.11) Ozols, et al. Gynecol Oncol 103:1-6, 2006

  11. Ovarian Cancer: Biologic Opportunities • Unique Biology of the Müllerian Epithelium and Peritoneal Cavity • Specialized relationship; spread via implantation • Frequent production of ascites, associated with VEGF • Negative immunoregulation (VEGF, IL-10, IL-6, IL-12, APC) • Growth Factor Receptors • EGF-R frequently expressed, mutations uncommon, frequency of overexpression variable • HER2/neu frequently expressed, high-level overexpression <15%, gene amplification uncommon • ER/PR/AR frequently expressed, variable functionality • Other receptors less well characterized • Growth Factor Production • Frequent high-level expression of VEGF • Increased expression of IL10, IL6, TNF, TGFα

  12. GOG-DTC: Ovary, Biologic Studies

  13. GOG0170D: Bevacizumab Phase II • Epithelial Ovarian Cancer • ≤ 2 Prior Therapies • RECIST Measurable • PS 0,1 • Two-stage accrual design • Primary endpoint PFS @6 m I Bevacizumab 15 mg/kg q3wk • Overall response rate 12/62 (19.4%), including 3 CR • 42% of pts alive and free of progression at 6 m • Median number of cycles = 7, range = 1 to 29 Open: Apr-02 Closed: Aug-04 Accrual: 62 pts Burger et al., Proc Ann Meet ASCO 24:A5009

  14. GOG0170-D (n = 62) PFS @ 6 m = 0.42 GOG0126 Series (n = 220) Platinum-Resistant Disease PFS @ 6 m = 0.16 (SE 0.025) GOG0170D: Bevacizumab Phase II Burger et al., Proc Ann Meet ASCO 24:A5009

  15. GOG218: Ovarian (stage III-IV) • Epithelial Ovarian or Primary Peritoneal Cancer • Suboptimal Cytoreduction • Collaborative design (GOG, NCI, Genentech) Paclitaxel 175 mg/m2 (3 h) Carboplatin AUC=6.0 Placebo q21d* Placebo (14 m total) I x 6 Placebo (14 m total) Paclitaxel 175 mg/m2 (3 h) Carboplatin AUC=6.0 Bevacizumab 15 mg/kg q21d* II x 6 Bevacizumab (14 m total) Paclitaxel 175 mg/m2 (3 h) Carboplatin AUC=6.0 Bevacizumab 15 mg/kg q21d* III x 6 *starting with C2 Open: 26-Sep-05 Closed: --- Target Accrual: 2000 pts (3 Y) Burger, et al.

  16. If IP Therapy is Really So Important… • Why has it been more than 2 years without an active GOG phase III trial for women with ovarian cancer and optimal cytoreductive surgery? • Where is the funding to support scientific investigation of IP therapy using generic off-patent medications (cisplatin and paclitaxel)? • Should our patients commit to increased toxicity and 2-3 days in the hospital with each cycle of “recommended” therapy? • Are we prepared to evaluate all new agents “IP” and “IV”? • Should IP therapy have a higher priority than evaluation of targeted agents, immunomodulation, and tumor molecular profiling?

  17. Revised 14-Oct-2006 NCI Clinical Announcement (05-JAN-2006) two cycles of ^ and potential risks ^ compared to standard IV chemotherapy ^ some ^ route ^ such as GOG0218 and ICON7, ^

More Related