Nivolumab and sunitinib combination in advanced soft tissue sarcomas : A multicenter, single-arm, phase Ib/II trial
Martin-Broto, J. (Universidad de Sevilla)
Hindi, Nadia (Universidad de Sevilla)
Grignani, G. (Candiolo Cancer Institute)
Martinez-Trufero, J. (Hospital Universitario Miguel Servet (Saragossa))
Redondo, A. (Hospital Universitario La Paz (Madrid))
Valverde, Claudia (Vall d'Hebron Institut d'Oncologia)
Stacchiotti, S. (Istituto Nazionale Tumori)
López Pousa, Antonio (Institut d'Investigació Biomèdica Sant Pau)
D'Ambrosio, L. (Candiolo Cancer Institute)
Gutierrez, A. (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Perez-Vega, H. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Encinas-Tobajas, V. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
De Álava, Enrique (Universidad de Sevilla)
Collini, Paola (Istituto Nazionale Tumori)
Peña-Chilet, M. (Hospital Virgen Del Rocio)
Dopazo, J. (Hospital Virgen Del Rocío)
Carrasco-Garcia, I. (Universidad de Sevilla)
Lopez-Alvarez, M. (Universidad de Sevilla)
Moura, D.S. (Universidad de Sevilla)
Lopez-Martin, Jose A (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab). This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37. 5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level-1 with sunitinib 37. 5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1. 1 (phase II). From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37. 5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4-26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3-4 adverse events included transaminitis (17. 3%) and neutropenia (11. 5%). Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Clinical trials as topic ; Immunotherapy ; Sarcoma ; Translational medical research
Published in:	Journal for immunotherapy of cancer, Vol. 8 Núm. 2 (17 2020) , p. e001561, ISSN 2051-1426

DOI: 10.1136/jitc-2020-001561
PMID: 33203665

11 p, 529.4 KB

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