Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial
Por:
Martin-Broto, J, Hindi, N, Grignani, G, Martinez-Trufero, J, Redondo, A, Valverde, C, Stacchiotti, S, Lopez-Pousa, A, D'Ambrosio, L, Gutierrez, A, Perez-Vega, H, Encinas-Tobajas, V, de Alava, E, Collini, P, Pena-Chilet, M, Dopazo, J, Carrasco-Garcia, I, Lopez-Alvarez, M, Moura, DS, Lopez-Martin, JA
Publicada:
1 ene 2020
Resumen:
Background 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). Methods 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). Results 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%). Conclusions 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.
Filiaciones:
Martin-Broto, J:
Univ Hosp Virgen del Rocio, Dept Med Oncol, Seville, Spain
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Hindi, N:
Univ Hosp Virgen del Rocio, Dept Med Oncol, Seville, Spain
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Grignani, G:
Candiolo Canc Inst, Div Med Oncol, FPO IRCCS Str Prov 142,Km 3,95, I-10060 Candiolo, TO, Italy
Martinez-Trufero, J:
Miguel Servet Univ Hosp, Dept Med Oncol, Zaragoza, Spain
Redondo, A:
Hosp Univ La Paz, Dept Med Oncol, Madrid, Spain
Valverde, C:
Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain
Stacchiotti, S:
Fdn Ist Ricovero & Cura Carattere Sci IRCCS Ist N, Dept Canc Med, Via Venezian 1, Milan, Italy
Lopez-Pousa, A:
St Pau Hosp, Dept Med Oncol, Barcelona, Spain
D'Ambrosio, L:
Candiolo Canc Inst, Div Med Oncol, FPO IRCCS Str Prov 142,Km 3,95, I-10060 Candiolo, TO, Italy
Gutierrez, A:
Univ Hosp Son Espases, Dept Med Hematol, Mallorca, Spain
Perez-Vega, H:
Univ Hosp Virgen del Rocio, Dept Radiol, Seville, Spain
Encinas-Tobajas, V:
Univ Hosp Virgen del Rocio, Dept Radiol, Seville, Spain
de Alava, E:
Univ Seville, Inst Biomed Sevilla IBiS, Virgen del Rocio Univ Hosp, CSIC,CIBERONC, Seville, Spain
Univ Seville, Sch Med, Dept Normal & Pathol Cytol & Histol, Seville 41009, Spain
Collini, P:
Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Soft Tissue & Bone Pathol Histopathol & Pediat Pa, Diagnost Pathol & Lab Med Dept, Ist Nazl Tumori, Milan, Italy
Pena-Chilet, M:
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Hosp Virgen del Rocio, Clin Bioinformat Area, Fdn Progreso & Salud FPS CDCA, Seville, Spain
Hosp Virgen del Rocio, Bioinformat Rare Dis BiER, Ctr Invest Biomed Red Enfermedades Raras CIBERER, FPS, Seville, Spain
Dopazo, J:
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Hosp Virgen del Rocio, Clin Bioinformat Area, Fdn Progreso & Salud FPS CDCA, Seville, Spain
Hosp Virgen del Rocio, Bioinformat Rare Dis BiER, Ctr Invest Biomed Red Enfermedades Raras CIBERER, FPS, Seville, Spain
Hosp Virgen del Rocio, INB ELIXIR es, FPS, Seville, Spain
Carrasco-Garcia, I:
Univ Hosp Virgen del Rocio, Dept Med Oncol, Seville, Spain
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Lopez-Alvarez, M:
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Moura, DS:
Univ Seville, Inst Biomed Sevilla IBIS, HUVR, CSIC, Seville, Spain
Lopez-Martin, JA:
Hosp 12 Octubre, Dept Med Oncol, Madrid, Spain
Inst Invest Sanitaria Hosp 12 Octubre I 12, Madrid, Spain
Gold, Green Published
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