Endometrial Committee 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.

Resected Endometrial GOG0249: A 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 (23 Mar 2009) –RTOG

Resected Endometrial PORTEC 3: Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma –MaNGO, ANZGOG, NRCI, NCIC-CTG, NSGO

Resected Endometrial GOG258 (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 Cancer (29 Jun 2009) –RTOG

Study proposal Proposed new study exploring if the combination of RT and CT is superior to CT: After 4 - A Phase III intergroup trial on adjuvant therapy in radically operated endometrial cancer patients (FIGO stage IC-IIIC) with high risk for micrometastatic disease NSGO Pooled survival data The combination of RT + CT is better than RT Results of previous studies: Thomas Hogberg, Lund Univ Hosp Oct 2009

PORTEC-3 Unless there is something fundamentally wrong with NSGO-9501/EORTC PORTEC-3 will most probably show that CMT is better than RT When PORTEC-3 is published CMT will probably become standard treatment The question about the contribution of RT will remain unanswered We have a time-frame in which we can resolve the question of the value of addition of radiotherapy to chemotherapy

Radical surgery TAH+BSO±LA CTx4 Primary endpoint Overall survival (OS) CTx2 RT Randomization Main inclusion criteria a. Endometrioid carcinoma b. Stage 1C grade 3 c. Stage IIA grade 3 and MI≥50%, IIB d. Stage IIIA-C Radical surgery, LA recommended but optional Main exclusion criteria Serous or clear cell carcinoma IIIA with only pos fluid cytology CT : Paclitaxel 175 mg/m 2, carboplatin AUC 5-6 (calculated) q 3 weeks N=1000 Proposed study Thomas Hogberg, Lund Univ Hosp Oct 2009

Pelvic Recurrence 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 –RTOG, NCRI, SWOG

Advanced/Recurrent NCIC: EN 8: Randomized Phase III Study of progestational hormone therapy versus deforolimus in women with recurrent or metastatic endometrial cancerEN 8 –ACRIN, AGO-AUST, AGO-OVAR, ANZOG, EORTC, GEICO, GINECO, JGOG, MANGO, MITO, NCRI, NSGO, SWOG

EN.8 - A PHASE III STUDY OF STANDARD THERAPY VERSUS RIDAFOROLIMUS IN WOMEN WITH RECURRENT OR METASTATIC ENDOMETRIAL CANCER WHO HAVE PREVIOUS HAD CHEMOTHERAPY Interested Groups: ACRIN, AGO-AUST, AGO-OVAR, ANZGOG?, DUTCH GOG, EORTC, GEICO, GINECO, JGOG, MANGO, MITO, NCRI, NSGO, SWOG

Proposed Design Change Accrual to the phase 2 studies has been slower than expected. Reasons: start up for centres, increasing use of prior chemotherapy in preference to hormonal agent. Consider allowing either hormonal OR chemotherapy as the control arm for this study.

Schema Sample size: Approximately 460 patients Arm 2: medroxy progesterone 200 mg or megestrol 160 mg (as per local practice) po daily Chemotherapy options Survival follow-up Disease progression Imaging q 8 weeks Arm 1: ridaforolimus 40 mg po days 1-5 each week RANDOMIZERANDOMIZE Women with recurrent or metastatic endometrial cancer 1-2 Prior Chemotherapy

Carcinosarcoma GOG0261: Randomized Phase III Trial of Carboplatin plus Paclitaxel versus Ifosfamide plus Taxol in Patients with Advanced, Persistent or Recurrent Carcinosarcoma NCRI, GINECO, JGOG, RTOG

Leiomyosarcoma GOG0250: Randomized Phase III Evaluation of Docetaxel, Gemcitabine, & G-CSF +/- Bevacizumab in the Treatment of Recurrent or Advanced Leiomyosarcoma

GTN Charge from the Executive RFP ISSTD

GTD Concepts Hydatidiform Mole Registry (Quinn) Pulse Act-D vs. 8 day MTX for Low Risk GTN