1475PD - A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide and cisplatin (API), followed by radiotherapy versus radiotherapy...

Date 11 September 2017
Event ESMO 2017 Congress
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Sarcoma
Surgery and/or Radiotherapy of Cancer
Presenter Patricia Pautier
Citation Annals of Oncology (2017) 28 (suppl_5): v521-v538. 10.1093/annonc/mdx387
Authors P. Pautier1, C. Brard2, A. Floquet3, L. Gladieff4, M. Rios5, S. Piperno-Neumann6, D. Berton-Rigaud7, J. Blay8, M. Fabbro9, J. Lotz10, A. Vinceneux11, F. Bertucci12, T. De La Motte Rouge13, C. Guillemet14, C. Genestie15, F. Duffaud16
  • 1Department Of Cancer Medicine, Institut de cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 2Department Of Biostatistics, Institut de cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 3Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 4Medical Oncology, Institut Universitaire du Cancer -Toulouse- Oncopole, 31059 - Toulouse/FR
  • 5Medical Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, 54519 - Vandoeuvre les Nancy/FR
  • 6Medical Oncology, Institut Curie, 75248 cedex5 - Paris/FR
  • 7Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - Saint-Herblain/FR
  • 8Medical Oncology, Centre Leon Berard, 69008 - Lyon/FR
  • 9Medical Oncology, ICM Regional Cancer Institute of Montpellier, 34298 - Montpellier/FR
  • 10Medical Oncology, APHP, CancerEst, Tenon University Hospital, 75020 - Paris/FR
  • 11Medical Oncology, CHRU Bretonneau, 37044 - Tours/FR
  • 12Medical Oncology, Institut Paoli Calmettes, 13274 - Marseille/FR
  • 13Medical Oncology, Centre Eugène Marquis, Rennes/FR
  • 14Medical Oncology, Centre Henri Becquerel, 76038 - Rouen/FR
  • 15Department Of Pathology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 16Medical Oncology, CHU La Timone Adultes, 13385 - Marseille/FR

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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

NCT00162721

Legal entity responsible for the study

Institut de Cancérologie Gustave Roussy

Funding

Association pour la Recherche contre le Cancer; Chugaï Pharma

Disclosure

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.