Memorial Sloan-Kettering Cancer Center, New York, NY

1. Adjuvant gemcitabine plus docetaxel for completely resected stage I-IV high grade uterine leiomyosarcoma: results of a phase II trial Martee L. Hensley, Nicole Ishill, Robert Soslow, Nadeem Abu-Rustum, Paul Sabbatini, Jason Konner, William Tew, David Spriggs, Carol A. Aghajanian Memorial Sloan-Kettering Cancer Center, New York, NY

2. RATIONALE • 2-year progression-free survival (PFS) is estimated at 20-40% for women with completely resected HGuLMS • Recurrence rates estimated at 50-80% • No prospective trials have adequately assessed adjuvant systemic therapy for high-risk disease

3. RATIONALE • Fixed dose-rate gemcitabine + docetaxel achieves high response rates in metastatic HGuLMS, even as 2nd or 3rd line therapy • Need to determine whether 2-year PFS with adjuvant chemotherapy for HGuLMS is sufficiently promising to warrant study in a prospective, randomized phase III trial

4. Gemcitabine-Docetaxel in advanced uterine LMS Hensley, JCO 2002; Hensley Gyn Onc 2008; Hensley Gyn Onc 2008

5. Background: historical PFS for uLMS

7. Small studies of adjuvant chemotherapy

8. OBJECTIVES Primary: • determine whether treatment with adjuvant fixed-dose-rate gemcitabine plus docetaxel following complete resection of stage I-IV high grade uterine LMS is associated with a >40% PFS at 2 years Secondary: • assess tolerability of 4 cycles fixed-dose-rate gemcitabine plus docetaxel in an adjuvant treatment population

9. Confirm histology: high-grade uterine LMS, stage I, II, III, or IV, completely resected Confirm No Evidence of Disease (NED) by CT C/A/P and physical examination Gemcitabine 900mg/m2 over 90 minutes days 1 and 8 + Docetaxel 75mg/m2 d8, with GCSF or Neulasta day 9, every 3 weeks for 4 cycles CT scan and Physical Exam every 3 months Study Schema

10. ELIGIBILITY CRITERIA • Pathologically confirmed uterine LMS, stage I, II, III, or IV, completely resected • No prior chemotherapy for LMS; no prior gemcitabine or docetaxel • Age > 18 y; KPS > 80% • Adequate organ function and bone marrow reserve • No prior radiation therapy (RT) to abdomen or whole pelvis • No other cancer present within the past 3 years • No neuropathy greater than grade 1

11. PATIENT CHARACTERISTICS

12. GRADE 3/4 TOXICITIES All patients completed all 4 cycles of planned therapy

13. Median follow-up for all patients = 49 months Median follow-up for Stage I, II patients = 40 months Progression-free survival

14. Median PFS-all patients = 13 mo

15. Median PFS-Stage I and II = 39 mo

16. Median Overall survival- all patients = not yet reached (> 45 mo)

17. Median Overall survival- Stage I, II patients = not reached (>60 months)

18. Sites of 1st Recurrence

19. CONCLUSIONS • Patients treated with adjuvant fixed-dose-rate gemcitabine + docetaxel for completely resected stage I-IV high-grade LMS had 2 year PFS of 45% • Patients with stage I or II disease had 2 and 3-y PFS of 59% • 2 year PFS appears superior to historical rates of 20-40% PFS at 2 years. • Median OS for all patients is not yet reached—exceeds 45 months • Assessment of adjuvant Gem-Doce therapy in high-risk stage I and II uterine LMS is warranted

20. REFERENCES • Omura, J Clin Oncol 3: 1240-1245, 1985 • Major, Cancer 71: 1702-1709, 1993. • Gaducci, Gyn Oncol 62: 25-32, 1996. • Kushner, Gyn Oncol 78: 221-227, 2000. • Pautier, Cancer 88: 1425-1431. 2000. • Hensley, J Clin Oncol 20: 2824-2831, 2002. • Hensley, Gyn Oncol 109: 323-328, 2008 • Hensley, Gyn Oncol 109: 329-324, 2008. • Giuntoli, Gyn Oncol 89: 460-469, 2003. • Pautier, Int J Gyn Cancer 14: 1112-1117, 2004. • Dinh, Gyn Oncol 92: 648-652, 2004. • Wu, Gyn Oncol 100: 166-172, 2006.

21. Carol Aghajanian, MD David Spriggs, MD GMO physicians and care team MSO physicians Robert Soslow, MD Kathy Appollo, RN GOG Uterine Corpus and DTC committees Laurence Baker, MD and SARC leadership CTOS leadership MSKCC patients and GOG patients and physicians Acknowledgments