IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Emanuela Palmerini , Antonio Lopez-Pousa , Giovanni Grignani , Andres Redondo , Nadia Hindi , Silvia Stacchiotti , Ana Sebio , Jose A. Lopez-Martin , Claudia Maria Valverde Morales , Javier Martinez-Trufero , Antonio Gutierrez , Enrique de Alava , Lorenzo D'Ambrosio , Paola Collini , Piero Picci , Paolo Giovanni Casali , Javier Martin Broto
Background: Herein, we present the results of the cohort on advanced bone sarcoma patients of the phase II part of the IMMUNOSARC study (NCT03277924), a European multicentre phase I-II trial aimed at investigating the activity of the combination of sunitinib (SU) and nivolumab (NI) in selected advanced sarcoma subtypes. Methods: Adult, pre-treated, progressing patients, ECOG 0-1, with a diagnosis of osteosarcoma, high-grade bone sarcoma, Ewing sarcoma, chondrosarcoma or dedifferentiated chondrosarcoma were eligible. SU 37.5 mg/day as induction was given days 1-14 and then reduced to 25mg/day continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (H1: PFSR 6-months: 15%). Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST v 1.1 and toxicity. Results: From Nov 2017 to Dec 2018, 40 eligible patients were included: (M/F = 27/13), median age 47 years (range 21-74), ECOG 0 in 11 (27%) cases, 36 (90%) were metastatic, 4 (10%) locally advanced. Histology: 17 osteosarcomas (43%), 14 chondrosarcomas (35%) (4 dedifferentiated), 8 Ewing sarcomas (20%), 1 bone undifferentiated pleomorphic sarcoma (2%). PFSR at 6 months based on local evaluation was 32%. At a median FU of 12.5 months (2-26), median PFS was 3.7 months (95% IC 3.4-4) while median OS was 14.2 months (95%CI: 7.1-21.3). OS rate at 3 and 6 months were 87% and 73%, respectively. ORR by RECIST: 1 CR (2.5%) (1 patient with dedifferentiated chondrosarcoma, lasting 22 months and on going), 1 PR (2.5%) (1 patient with osteosarcoma, lasting 5.7 months), 22 SD (55%, lasting > 6 months in 45% of the cases) and 16 PD (40%). G3/5 toxicities are detailed in Table. Conclusions: The trial met its primary endpoint in the cohort of patients with advanced bone sarcoma, with > 30% of patients free from progression at 6 months. Pre-planned tumor microenvironment genomic, exploratory analysis on pre and post-treatment tumor samples is on going. Clinical trial information: NCT03277924.
Toxicity | Grade 3-4 | Grade 5 |
---|---|---|
Neutropenia | 4 (10%) | 0 |
Anaemia | 4 (10%) | 0 |
ALT/AST increased | 3 (7.5%) | 0 |
Fatigue | 2 (5.0%) | 0 |
Oral mucositis | 2 (5.0%) | 0 |
Thrombocytopenia | 1 (2.5%) | 0 |
Dysphagia | 1 (2.5%) | 0 |
Gastric haemorrhage | 1 ( 2.5%) | 0 |
Malaise | 1 (2.5%) | 0 |
Thromboembolic event | 1 (2.5%) | 0 |
Pneumonitis (toxic death) | 0 | 1 (2.5%) |
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