Evaluation of hyperprogression in patients with sarcoma treated with targeted therapy and/or immunotherapy in early-phase clinical trials.

Abstract

11560 Background: Hyper-progressive disease (HPD) is an adverse outcome with acceleration of tumor growth, often accompanied by clinical deterioration. This phenomenon is described with immunotherapy (IT) but its incidence in sarcoma and/or in the context of targeted therapy (TT) remains unknown. Tumor growth rate (TGR) allows for dynamic evaluation of tumor volume change over time and may complement RECIST. We evaluated HPD in sarcoma patients (pts) treated in early-phase trials by assessing TGR and describing their subsequent clinical outcomes. Methods: We retrospectively reviewed medical records from advanced soft tissue sarcoma (STS) pts enrolled in early phase trials at the Princess Margaret Cancer Centre between January 2012 and December 2022. TGR was calculated based on tumor measurements taken at pre-baseline, baseline, and on-treatment CT scans. We used the Champiat formula (Clin Cancer Res 2017) to calculate TGR ratio. Primary objective was to describe the incidence of HPD, defined as a TGR ratio of > 50%. Secondary objective was to investigate the correlation between HPD with progression-free survival (PFS) and overall survival (OS). Results: We identified a total of 192 pts involved in STS early phase trials from 2012-2022. Most common histology was leiomyosarcoma seen in 72 pts. Eighty-four pts (43.8%) received TT, 75 (39%) pts received IT-based, and the rest had combined TT/IT regimens (n = 33, 17.2%). The incidence of HPD was 6.8% (n = 13), including IT-based (n = 9) and non-IT-based (n = 4) regimens. HPD was associated with a worse PFS, and OS compared to non-HPD pts (median PFS 1.6m vs 4.6m HR: 5.5, 95%CI 2.8-10.6, P < 0.001; median OS 5.5 vs 16.1 months; HR: 3.7, 95%CI: 2.0-7.1, P < 0.001). On multivariable analysis, only IT was significantly associated with HPD (OR 3.9, 95%CI: 1.1-13, P = 0.021). There was no association between HPD and new lesions or sarcoma histology subtype. Conclusions: HPD occurs in a small subset of sarcoma patients undergoing clinical trials with TT or IT. Exploring TGR provides clinically meaningful data as it pertains to HPD as it predicts OS and PFS in sarcoma patients undergoing early-phase clinical trials.