Abstract 4573: Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials
Authors: Groisberg Roman , Subbiah Vivek , Hong David , Janku Filip , Piha-Paul Sarina , Naing Aung , Benjamin Robert , Putal Shreyas Kumar , Somaiah Neeta , Conley Anthony 
Published: July 2017

Abstract
Background: Immunotherapies, specifically those based on immune checkpoint inhibitors, have shown promising activity in multiple tumor types. Other than the drug mifamurtide for osteosarcoma, there are currently no approved immunotherapies for sarcomas. We analyzed the outcome of patients with advanced sarcomas treated in immunotherapy phase 1 trials.
Methods: We analyzed the medical records of patients with advanced sarcoma who were referred to Phase 1 trials and had received at least one dose of an immunotherapy including checkpoint inhibitors, vaccines, or cytokine based therapies. Clinical parameters reviewed were age, histology, lactate dehydrogenase, albumin, metastatic sites, performance status, prior therapies, toxicity and response on imaging. Progression free survival (PFS) was measured from the date of the first dose to the date of progression on imaging.
Results: Among 50 patients enrolled in immunotherapy trials we found 14 different subtypes of sarcomas (Bone 10; Soft tissue 40). Patients were 42% male and 58% female. The median age was 53.5 years (18-84) and Royal Marsden Hospital (RMH) prognostic score was &lt;2 (86%). The Performance status (PS) was ECOG 0-1 in 48 patients (96%); the median number of prior therapies was 3 (range: 0-12). Immunotherapy consisted of checkpoint inhibitors in the majority of trials (82%: PD1 =8, PD-L1=10, CTLA4=22, other=1), as well as vaccines (14%), and cytokines (4%). The median overall survival (OS) was 13.4 months, 95% [CI] = (11.2 months to not reached). Median PFS was 2.4 months (95% CI = 1.9-3.2 months). Best response was partial response (PR) in 2 patients with alveolar soft part sarcoma (ASPS) and stable disease in 11 patients (3 GIST, 3 lipo (2 dedifferentiated, 1 well-differentiated), 2 ASPS, 2 leiomyo, 1 osteo). Patients were treated past progression per iRECIST criteria (32%). Pseudo-progression followed by response was observed in 3 patients (6%). Median OS was 24 months for patients (40%) with 0-2 prior therapies and for patients (60%) with &gt2 prior therapies was 8 months (P=0.001). Median OS was 24 months for RMH score 0 and was 12 months for patients with score 1-2 (P=0.08). Grade 3/4 adverse events included rash (10%), fever (6%), fatigue (6%), and nausea/vomiting (6%). Other toxicities included hypothyroidism, transaminitis, pancreatitis, pituitary apophysitis, pneumonitis and mucositis.
Conclusions: Immunotherapies were well tolerated in advanced sarcoma patients enrolled in trials. These patients had been heavily pretreated and had good performance status and favorable RMH prognostic scores. All ASPS patients had clinical benefit with checkpoint inhibitors and this was the only subtype with a partial response. Further evaluation of checkpoint inhibitors in sarcomas, especially ASPS, is warranted.
Citation Format: Roman Groisberg, Vivek Subbiah, David Hong, Filip Janku, Sarina Piha-Paul, Aung Naing, Robert Benjamin, Shreyas Kumar Putal, Neeta Somaiah, Anthony Conley. Characteristics and outcomes of patients with advanced sarcoma enrolled in early phase immunotherapy trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4573. doi:10.1158/1538-7445.AM2017-4573