The efficacy and safety of vincristine, irinotecan and anlotinib in Epithelioid Sarcoma

Abstract

Background: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients.

Methods: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People's Hospital treated with irinotecan (50 mg/m²/d d_1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021.

Results: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated.

Conclusions: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma.

Trial registration: This study was approved in the Medical Ethics Committee of Peking University People's Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Keywords: Epithelioid sarcoma; Objective response; Systemic treatment; Toxicity.

Fig. 1

An epithelioid sarcoma patient with primary lesion located at right finger (patient number 4 in table 2) developed lymphatic metastasis to right axillary fossa before the combination therapy of irinotecan, vincristine and anlotinib

Fig. 2

Partial Response was noticed shortly after 3 cycles of this combination therapy in the right axillary fossa lymph node metastasis (patient number 4 in Table 2)

Fig. 3

Manifestation of coronal scan of magnetic resonance imaging for the patient with right axillary fossa lymphatic metastasis before this combination treatment, who has progressed upon two lines of chemotherapy

Fig. 4

The magnetic resonance imaging manifestation after 3 cycles of irinotecan, vincristine and anlotinib, which induced shrink of the tumor as well as liquefactive necrosis

Fig. 5

The Kaplan-meier estimate survival curve for overall survival in this group of patients from diagnosis to death

Fig. 6

A female patients (patient number 5 in Table 2) with epithelioid sarcoma in right inguinal fold experienced tumor rupture in her retroperitoneum. This was her computerized tomography (CT) scan before rupture

Fig. 7

The CT scan taken shortly after her tumor rupture in her retroperitoneum with drainage tube after Emergent debridement surgery (patient number 5 in Table 2). Following debridement and suturing, this female patient recovered from the infection and continued using single chemotherapy of irinotecan