Gynecologic Oncology Group Gynecologic Oncology Group Uterine Corpus Trials: GCIG David Scott Miller, M.D., F.A.C.O.G., F.A.C.S. Director and Dallas Foundation Chair in Gynecologic Oncology Professor of Obstetrics & Gynecology University of Texas Southwestern Medical Center Dallas, Texas, U.S.A.

Gynecologic Oncology Group GOG0249 Eligible: Stage I-IIA endometrial carcinoma, with high-intermediate risk factors, Stage IIB (occult) endometrial carcinoma (any histology), with or without risk factors, and Stage I-IIB (occult) serous or clear cell endometrial carcinoma, with or without other risk features TREATMENT RANDOMIZATION Regimen I: Pelvic Radiation Therapy (4500/25 fractions-5040 cGy/28 fractions) over 5-6 weeks Optional Vaginal Cuff Boost ONLY for Stage II patients and Stage I patients with papillary serous and clear cell carcinomas OR Regimen II: Vaginal Cuff Brachytherapy + 3 cycles of chemotherapy consisting of Paclitaxel 175 mg/m2 (3hr) + Carboplatin AUC 6 q 21 days chemotherapy to start within 3 weeks of initiating brachytherapy

Gynecologic Oncology Group PHASE III TRIAL OF PELVIC RADIATION THERAPY VERSUS VAGINAL CUFF BRACHYTHERAPY FOLLOWED BY PACLITAXEL/CARBOPLATIN CHEMOTHERAPY IN PATIENTS WITH HIGH RISK, EARLY STAGE ENDOMETRIAL CANCER

Gynecologic Oncology Group GOG0249 Objectives –Recurrence free survival –Survival –Patterns of failure –QOL Stats –49% decrease in recurrence/death –85% > 92% 3 yr RFS –N = 562 Activated 23 Mar 2009

Gynecologic Oncology Group Uterine Corpus Committee GOG0249: BIQSFP UC, QOL & CEM collaboration

Gynecologic Oncology Group Uterine Corpus Committee 0184R GOG0258 (UC0704): A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma

Gynecologic Oncology Group GOG258

Gynecologic Oncology Group GOG0258 Enroll patients with either surgical stage III or IVA endometrial carcinoma TREATMENT RANDOMIZATION REGIMEN I: Cisplatin 50 mg/m2 IV Days 1 and 28plus Volume-directed radiation therapy forfollowed by Carboplatin AUC 6 plus Paclitaxel 175 mg/m2 q 21 days for 4 cycles Or REGIMEN II: Carboplatin AUC 6 plus Paclitaxel 175 mg/m2 q 21 days for 6 cycles

Gynecologic Oncology Group GOG0258 Objectives –Recurrence free survival –Survival –Adverse effects Stats –28% decrease recurrence/death –61% > 70% 3 yr RFS –N = 804

Gynecologic Oncology Group Uterine Corpus Committee Pelvic Recurrence has resulted in: –TAH-BSO lymphadenectomy alone –fewer using adjuvant WPRT GOG0238: A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients With Pelvic- Only Recurrence of Carcinoma of the Uterine Corpus

Gynecologic Oncology Group GOG 0238

Gynecologic Oncology Group GOG0238 Objectives –PFS –Sites of recurrence –OS Stats –Phase II-III –Interim analysis > 60 failures –Opened Feb ‘08 –N = 164

Gynecologic Oncology Group 209R DTM0834: A three arm randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/everolimus and ixabepilone/carboplatin as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer

Gynecologic Oncology Group Uterine Corpus Committee 188R GOG0250 Randomized Phase II Trial of Temsirolimus or the Combination of Hormonal Therapy & Temsirolimus in Women With Advanced or Recurrent Endometrial Cancer

Gynecologic Oncology Group Uterine Corpus Committee 150R & 161R GOG0261 (UC0701): Randomized Phase III Trial of Carboplatin plus Paclitaxel versus Ifosfamide plus Taxol in Patients with Advanced, Persistent or Recurrent Carcinosarcoma

Gynecologic Oncology Group GOG0261

Gynecologic Oncology Group GOG261 Objectives –OS –PFS –Toxicity –QOL Stats –Noninferiority –Death rate < 11% –N = 415, (264 deaths)

Gynecologic Oncology Group Uterine Corpus Committee Future plans: Leiomyosarcoma GOG0250: Randomized Phase III Evaluation of Docetaxel, Gemcitabine, & G-CSF +/- Bevacizumab in the Treatment of Recurrent or Advanced Leiomyosarcoma

Gynecologic Oncology Group Uterine Corpus Committee Future plans: Leiomyosarcoma SCHEMA Enroll patients with uterine LMS, measurable disease, no prior cytotoxic therapy STRATIFY for prior whole pelvic radiation Then RANDOMIZE to: REGIMEN I: Gemcitabine 900 mg/m2 IV over 90 minutes days 1 and 8 plus Docetaxel 75 mg/ m2 IV over 60 minutes day 8 every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy or REGIMEN II: Gemcitabine 900 mg/m2 IV over 90 minutes days 1 and 8 plus Docetaxel 75 mg/ m2 IV over 60 minutes day 8 plus Bevacizumab 15 mg/kg IV over 90 minutes day 1 every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy GOG0250

Gynecologic Oncology Group GOG0250 Objectives –PFS –RR –OS –Toxicity Stats –40% increase PFS –4 > 6.7 mos –N = 130

Gynecologic Oncology Group A Phase II Study to Determine the Response to Second Curettage as Initial Management for Persistent Low Risk, Non-Metastatic Gestational Trophoblastic Neoplasia

Gynecologic Oncology Group Concept Biweekly dactinomycin now needs to be tested against 8-day MTX/FAR, arguably the most commonly used regimen worldwide. The 8-day regimen has a similar primary response but a vastly different cost, resource and utility profile, and it has never been subjected to the scrutiny of a multi-centred RCT.