2018 ASCO Annual Meeting!
Session: Plenary Session Including the Science of Oncology Award and Lecture
Type: Plenary Session
Time: Sunday June 3, 1:00 PM to 4:00 PM
Location: Hall B1
Maintenance low-dose chemotherapy in patients with high-risk (HR) rhabdomyosarcoma (RMS): A report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).
Pediatric Solid Tumors
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr LBA2)
Author(s): Gianni Bisogno, Gian Luca De Salvo, Christophe Bergeron, Meriel Jenney, Johannes H.M. Merks, Veronique Minard-Colin, Daniel Orbach, Heidi Glosli, Julia Chisholm, Michela Casanova, Soledad Gallego Melcon, Andrea Ferrari, European Paediatric Soft Tissue Sarcoma Study Group (EpSSG); Department of Women and Children Health, University Hospital of Padova, Padova, Italy; Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Institut d'Hematologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France; Department of paediatric oncology, Children’s Hospital for Wales, Cardiff, GB; Emma Children’s Hospital-Academic Medical Center (EKZ-AMC), Amsterdam, Netherlands; Gustave Roussy, Villejuif, France; Institut Curie, Paris, France; Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Children and Young People’s Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; University Hospital Vall d’Hebron, Barcelona, Spain; Istituto Nazionale per lo Studio e la Cura dei Tumori - IRCCS, Milan, Italy
Background: Most patients with localized RMS achieve complete remission during standard (std) treatment but approximately 20-30% of them relapse and chance of salvage is poor. We tested whether adding maintenance metronomic chemotherapy after std chemotherapy would improve survival for patients with non metastatic RMS defined as HR according to EpSSG stratification. Methods: Patients (pts) age >6 months <21 years, with N0 alveolar (A)RMS or incompletely resected (Group II or III) embryonal (E)RMS arising in an unfavorable primary site and/or N1 in complete remission after std treatment including 9 cycles of ifosfamide, vincristine and actinomycin D +/- doxorubicin, surgery and/or radiotherapy were eligible for randomization to stop treatment (Std-arm) or receive maintenance chemotherapy (M-arm) with 6 28-day cycles of iv vinorelbine 25 mg/m2 on day 1,8,15 of each cycle and continuous daily oral cyclophosphamide 25 mg/m2 . The study was initially designed with 80% power (5% 2-sided alpha level) to detect an increase in 3 yr Event Free Survival (EFS) from 55% to 67%, a Hazard Ratio of 0.67, but was successively amended to allow a detection of a relative reduction in the relapse rate of 50% in the M-arm, with 80% power, testing at the 5% significance level (2-sided). Results: 670 pts were entered between 4/2006-12/2016, with 371 confirmed eligible and 186 assigned to the std-arm and 185 to M-arm. Clinical features were well balanced in the two arms and included ERMS 67%, ARMS 33%, age 10+ years 21%; IRS Group III 86%; N1 16%. Most common primary tumor sites were parameningeal (32%) and “other” sites (23%). With median follow up of 5 years in surviving pts, 3 yr EFS and overall survival (OS) in M-arm vs Std-arm were respectively: EFS 78.4% (95% IC -71.5-83.8) vs 72.3% (95% IC -65.0-78.3) (p 0.061) and OS 87.3% (95% IC 81.2-91.6) vs 77.4 (95% IC 70.1-83.1) (p = 0.011). Toxicity in the M-arm was manageable: grade 3/4 febrile neutropenia in 25% of pts, grade 4 neurotoxicity in 1.1%. Conclusions: The addition of maintenance after std treatment significantly improves OS in HR RMS patients and support its inclusion in future EpSSG trials. Clinical trial information: 2005-000217-35.