In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 11527-11527
Abstract:
11527 Background: Overexpression of ABCB1/P-glycoprotein (Pgp) predicts poor outcome in retrospective osteosarcoma series.Two prospective trials with Pgp expression and post-induction histologic response as stratification factors were activated in Italy (ISG/OS-2) and Spain (GEIS-33). Methods: Patients ≤ 40 years with extremity non-metastatic high-grade osteosarcoma were eligible. Analysisi of Pgp expression from diagnostic biopsy was centralized. Preoperatively, all patients received methotrexate, adriamycin, cisplatinum (MAP). Surgery was performed at week 8. All patients received a dose of adriamycin following surgery. In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months then weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor histologic response (necrosis 〈 90%) to MAP. Patients without overexpression of Pgp (Pgp-) received MAP postoperatively, regardless the pathological response. From March 2013, an amendment increased high dose methotrexate cumulative dose from 60 g/m2 (5 cycles) to 120 mg/m2 (10 cycles). The post-amendment regimen was adopted in the observational prospective study by GEIS. Here we present the merged analysis of ISG/OS-2 patients treated post-amendment and GEIS-33. Results: From March 2013 to April 2018, 274 patients were included. Median age was 14 years (range 4-38), male/female: 163/111; 90 were Pgp-, 164 were Pgp+, 20 not evaluable. With a median follow-up of 48 months (1.3-78.5 months), the 3-year EFS and OS were 71.9% (95%CI 66-76.9) and 88% (95%CI: 83.2-91.5) respectively, with no inferior survival for Pgp positive patients and improved survival for good responders (Table). Conclusions: In this prospective uncontrolled study with a risk-adapted strategy for non-metastatic osteosarcoma, survival is superior to that of all ISG/GEIS previous series. The 3-year EFS of 71.9% compares favorably with other reports. Pgp+ patients performed well in this study, in which mifamurtide and HDIFO were added after a poor response to MAP. Clinical trial information: NCT01459484; NCT04383288. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2021.39.15_suppl.11527
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2021
detail.hit.zdb_id:
2005181-5