There is no proven benefit of adjuvant treatment in uterine sarcoma (US). SARCGYN was a phase-III study which compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B). The study met its primary end point (3-year progression-free survival (PFS)) and showed a statistical increase of the 3-year PFS in the chemo+RT arm (A) vs radiation arm (B) (55% and 41% respectively, [P = 0.048]) after a median follow-up of 4.3 years (Ann Oncol 2013). Secondary end-point was overall survival (OS) that required a longer follow-up.
Patients with FIGO stage ≤III US, and physiological age ≤65 years were randomized after complete surgery and normal thoracic, abdominal and pelvic CT scans between CT and no CT, with a stratification between carcinosarcomas (CS) versus others. Study was stopped earlier because of lack of recruitment. All patients received pelvic RT (45 grays); vaginal brachytherapy was optional. Chemotherapy consisted in four cycles of doxorubicin 50 mg/m2, d1; ifosfamide 3 g/m2/day d1-2; cisplatin 75 mg/m2, d3; + G-CSF q 3 weeks.
Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, and 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, and 19 carcinosarcomas. API was toxic with two toxic deaths and one acute leukemia. After a median FU of 9.9 years [0.3-15.1], 42/81 patients relapsed, 16 in arm A, and 26 in arm B, and 38 died, 16 in arm A, and 22 in arm B. The 5-year OS is 74% in arm A and 60% in arm B, and the difference is not significant (p = 0.16).
In this trial interrupted at an early stage and with a longer follow-up, there is no statistical impact of API adjuvant CT on OS. The two toxic deaths and the integration of carcinosarcomas may have impacted on the global prognosis. A selection of a specific uterine population and a less toxic chemotherapy for future studies are mandatory.
Clinical trial identification
Legal entity responsible for the study
Institut de Cancérologie Gustave Roussy
Association pour la Recherche contre le Cancer; Chugaï Pharma
P. Pautier: Advisory board: Roche and Pharmamar. S. Piperno-Neumann: Travel grants PharmaMar, Novartis. F. Bertucci: Traveling grants, PharmaMar, Novartis. F. Duffaud: Consultancy work: Lilly, Pharmamar, Bayer, Novartis Travel grants: Pfizer, Pharmamar. All other authors have declared no conflicts of interest.