Virgen del Rocio University Hospital, Institute of Biomedicine Research (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain
Javier Martin Broto , Nadia Hindi , Andres Redondo , Javier Martinez-Trufero , Silvia Stacchiotti , Emanuela Palmerini , Enrique Alava , David Silva Moura , Herminia Perez Vega , Irene Otero , Patricio Ledesma , Emanuela Marchesi , Jose A. Lopez-Martin
Background: Disruption of angiogenesis substantially enhances the efficacy of immune-based cancer therapies. The combination of an antiangiogenic drug (sunitinib or pazopanib) plus anti- PD1 (nivolumab) exhibited both higher activity and toxicity compared with antiangiogenic drug alone in renal cell carcinoma (RCC). We hypothesized that sunitinib (SU) and nivolumab (NI) could be synergistic in some sarcoma subtypes and the toxicity profile could be different from RCC. We present the results of phase I part of the combination of SU-NI in advanced sarcoma patients (pts). Methods: Pretreated progressing pts, ECOG 0-1 and diagnosed with UPS, synovial sarcoma (SS), clear cell sarcoma (CCS), angiosarcoma (AS), epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), osteosarcoma (OS), Ewing sarcoma (EWS) or dedifferentiated chondrosarcoma (DCh) were eligible. SU 37.5 mg/d as induction was given for the first 14 days. The dose-finding stage (from day 15 to 45) would be completed when 10 dose limiting toxicity (DLT)-evaluated pts had been treated with DLT rate < 0.33. Two level- doses were designed: (0 initial) SU 37.5 mg/d or (-1) SU 25 mg/d along with NI 3 mg/kg/2w for both. SU-NI was maintained up to progression or intolerance. Results: From May to October 2017, 16 pts (M/F 10/6), median age 38y (25-78) were enrolled. Diagnosis was: CSS in 4 (25%), ASPS in 3 (19%); AS, OS, SS (2 each, 12.5%); UPS, extraskeletal OS and Ch (1 each, 6%). There were three DLT in the first 6 pts at dose level 0 (G3 fatigue in 2 and G4 septic shock) and 1 DLT in the following 10 pts at level -1 (febrile neutropenia). G3/4 toxicity: fatigue 25%, thrombocytopenia 19%, mucositis 13% and neutropenia 13%. There were 6 RECIST PR (42.8%), 4 SD (2 of them 25% of shrinkage) and 4 PD in 14 evaluable pts. PR occurred in 2 CCS and in one of AS, Ch, SS, ASPS while 2 cases (ASPS and UPS) shrank 25%. Conclusions: At the RDP2 (SU 25 mg/d and NI 3 mg/kg/2w), SU-NI is a feasible combination with manageable toxicity. SU-NI has induced objective responses in several sarcoma subtypes. The study is currently on a phase II part. Clinical trial information: NCT03277924
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Abstract Disclosures
2020 ASCO Virtual Scientific Program
First Author: Emanuela Palmerini
2023 ASCO Annual Meeting
First Author: Lee D. Cranmer
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2022 ASCO Annual Meeting
First Author: David Silva Moura