Early clinical and metabolic response to tazemetostat in advanced relapsed INI1 negative epithelioid sarcoma

Abstract

Epithelioid sarcoma (ES) is a rare soft tissue sarcoma with an incidence of 0.05 per 100,000 population in the USA. It is characterized by multiple local recurrences and regional lymph nodes form the commonest site of metastases. The function of Integrase Inhibitor 1 (INI1) protein is lost in more than 90% of cases, which was the basis for the introduction of tazemetostat into the therapeutic armamentarium for management of advanced ES. The efficacy and manageable toxicity profile of tazemetostat have been demonstrated recently, leading to its accelerated approval for treatment of advanced ES. We report one of the first real-world cases of relapsed, metastatic ES treated with tazemetostat. The patient attained partial response with the therapy and is tolerating the drug well without serious toxicities.

Keywords: epigenetics; epithelioid sarcoma; personalized medicine; targeted therapy; tazemetostat.

Figure 1.. Histopathological images of the tumor with micropscopy and immunohistochemistry.

(A) Representative histophotomicrograph of the tumor showing cells with prominent nucleoli and moderate to abundant cytoplasm arranged in sheets showing epithelioid morphology. (B) Immunohistochemical stain for INI1 protein showing loss of its expression compared with positive internal control.

Figure 2.. PET scan imaging showing radiographic findings prior to starting tazemetostat.

(A & B) MIP image showing focal increased tracer uptake in the left inguinal region and the left knee joint region corresponding to cutaneous nodules at the amputated site of left tibia and fibula on CT showing increased FDG uptake on fused PET-CT. (C & D) Areas of sclerosis in the left tibia with increased FDG uptake. (E–G) Ulcerated left inguinal lymph nodes on CT showing increased FDG uptake on fused PET-CT. CT: Computed tomography; MIP: Maximum intensity projection.

Figure 3.. PET Scan imaging showing radiographic findings after treatment with tazemetostat.

(A) MIP image showing focal increased tracer uptake in the left inguinal region and in the left knee joint region. (B & C) Previously seen cutaneous nodules in baseline image show resolution in size and metabolic activity in the present study. (D & E) Ulcerated subcentimetric left inguinal lymph nodes on CT showing increased FDG uptake on fused PET-CT scan. (F & G) Sclerosis in left tibia showing decreased FDG uptake compared with previous scan with overall findings suggest partial resolution of the disease following therapy. CT: Computed tomography; MIP: Maximum intensity projection.