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1625MO ABCB1/P-glycoprotein (Pgp) expression as stratification factor for treatment of patients with non metastatic extremity high grade osteosarcoma: An Italian Sarcoma Group (ISG) multicentric prospective trial (ISG/OS-2)

2020; Elsevier BV; Volume: 31; Linguagem: Inglês

10.1016/j.annonc.2020.08.1851

1569-8041

Emanuela Palmerini, Cristina Meazza, A. Tamburini, Gianni Bisogno, Virginia Ferraresi, Sebastian Dorin Asaftei, Giuseppe Maria Milano, Luca Coccoli, Carla Manzitti, Roberto Luksch, Davide María Donati, Massimo Serra, Rossella Bertulli, Marco Gambarotti, C. Favre, Alessandra Longhi, Paolo G. Casali, Piero Picci, Franca Fagioli, S. Ferrari,

Immunotherapy and Immune Responses

Overexpression of ABCB1/P-glycoprotein (Pgp) predicts poor outcome in retrospective osteosarcoma series. Two prospective trials with Pgp expression as stratification factor were activated in Italy and Spain. Patients ≤ 40 years with extremity high-grade osteosarcoma were eligible. Pgp expression was centralized. Preoperatively, all patients received MAP (methotrexate, adriamycin, platinum). In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months than 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 response (PR) to MAP. Patients without overexpression of Pgp (Pgp-) received MAP postoperatively, regardless the pathological response. From March 2013, an amendment increased high dose methotrexate (HDMTX) cumulative dose from 60 g/m2 (5 cycles) to 120 mg/m2 (10 cycles). In the same period, this regimen was adopted in an observational prospective study performed by the Spanish Sarcoma Group (GEIS) (NCT04383288). From June 2011 to March 2018, 291 ISG patients were screened and 279 were included: 110 were Pgp-, 154 were Pgp+, while in 15 patients Pgp expression was not evaluable. With a median follow-up of 58 months (range 1.2 – 102.2), the 3-year EFS and OS were 65.5% (95% CI 59.4-70.9) and 85.8% (95% CI 81-89.6), respectively, with improved survival after 10 HDMTX cycles (table).Table: 1625MOn% 3-yrs EFS (95% CI)Pgp°0.0587Negative (MAP)11059.9 (49.8-68.7)Positive (mifamurtide+HDIFO if PR)15470.1 (62.1-76.8)Necrosis<0.0001Good response11680 (71.3-86.4)Poor response16355.1 (47-62.5)Amendment0.009Pre (5 HDMTX cycles)7457.6 (45.4–67.9)Post (10 HDMTX cycles)20568.4% (61.4-74.5)°not evaluable in 15 patients Open table in a new tab °not evaluable in 15 patients In this prospective uncontrolled study, EFS compared favorably with all our previous series. With a limited number of HDMTX cycles, EFS was suboptimal, and significantly improved after an amendment increasing HDMTX cycles to 10. Pgp+ patients performed well in this study, in which they were added mifamurtide and HDIFO after a PR to MAP: a pre-planned merged analysis of this study with a twin GEIS observational series is ongoing.