Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network

Smrke, Alannah; Frezza, Anna Maria; Giani, Claudia; Somaiah, Neeta; Brahmi, Mehdi; Czarnecka, Anna; Rutkowski, Piotr; Graaf, Winette van der; Baldi, Giacomo Giulio; Connolly, E.; Duffaud, Florence; Huang, Paul H.; Gelderblom, Hans; Bhadri, Vivek; Grimison, Peter; Mahar, Annabelle; Stacchiotti, Silvia; Jones, Robin L.

doi:10.1016/j.esmoop.2022.100522

Cited by 16 publications

(6 citation statements)

References 19 publications

(29 reference statements)

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“…After an early and aggressive local recurrence and before the correct anatomopathological diagnosis was made, our patient received chemotherapy with a combination of doxorubicin and ifosfamide [22], facilitating a salvage surgery. The response to doxorubicin-based chemotherapies has been only described as low, according to other published series, such as the retrospective series of 55 patients of A. Smrke et al [6], with a partial response of 12% (4/34) and stable disease of 44% (15/34) of the patients. However, our patient presented with a partial response that allowed surgical salvage of the disease, and it provides an example of how CCS patients can sometimes respond to traditional chemotherapy such as doxorubicin-ifosfamide chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The treatment of choice for localized CCS is wide surgical resection, although radiation therapy is used in some situations [5]. Chemotherapy is predominantly employed in patients with metastatic disease [5] and, despite the poor evidence to support their use in CCS cases, conventional systemic therapies such as doxorubicin, gemcitabine-based chemotherapy, and pazopanib are often used [6]. Also, inhibitors of the vascular endothelial growth factor receptor (VEGFR) pathway such as sunitinib, have demonstrated a response rate of 30% ( n = 3/10) in a retrospective study.…”

Section: Introductionmentioning

confidence: 99%

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A Clear Cell Sarcoma Case: A Diagnostic and Treatment Challenge, with a Promising Response to Trabectedin

Galera,

Álvarez,

Arregui

et al. 2023

Case Rep Oncol

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Introduction: Clear cell sarcoma (CCS) is a rare and aggressive soft tissue sarcoma. CCS is characterized by the translocation t(12;22) (q13;q12), involving the fusion of EWSR1 and ATF1 genes, and less frequently the fusion gene EWSR1-CREB1. Usually, CCSs are considered poorly responsive to conventional chemotherapy. However, trabectedin has shown activity against translocation-related sarcomas. Furthermore, preclinical results suggest that trabectedin is a promising antitumor agent for CCS, potentially inducing melanocytic differentiation. Case Presentation: We report the case of a challenging anatomopathological diagnosis in a patient with an aggressive metastatic CCS. Following the diagnosis of CCS, the patient experienced a clinical and radiological tumor response to trabectedin after four lines of treatment. Conclusion: This is a novel report of CCS treated with trabectedin that resulted in a partial response and suggests the need for further research on trabectedin as a therapeutic option for CCS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Clear Cell Sarcoma Case: A Diagnostic and Treatment Challenge, with a Promising Response to Trabectedin

Galera,

Álvarez,

Arregui

et al. 2023

Case Rep Oncol

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“…Current systemic therapies for clear cell sarcoma are of limited benefit ( 32 – 36 ). Tyrosine kinase inhibitors were given in the past to treat patients with CCS in different clinical trials including crizotinib ( 32 , 33 ), sorafenib ( 34 ) tivantinib ( 35 ) and sunitinib ( 33 , 36 ). Generally, responses were poor, partial and very short-lasting with only limited disease stabilization.…”

Section: Discussionmentioning

confidence: 99%

Case report: Robust response of metastatic clear cell sarcoma treated with cabozantinib and immunotherapy

Muskatel

Pillar²,

Godefroy³

et al. 2022

Front. Pediatr.

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Clear Cell Sarcoma (CCS), also referred to as malignant melanoma of soft parts, is a rare and aggressive malignant tumor. It comprises 1% of all soft tissue sarcomas and is known to be radio- and chemotherapy resistant. CCS shares morphological and immunohistochemical features with malignant melanoma, including melanin biosynthesis and melanocytic markers. However, it is distinct for the presence of EWSR1-ATF1 translocation which activates MITF transcription factor. We report here of an aggressive case of CCS in a 9-year-old patient, which demonstrates the critical role of molecular analysis in the diagnosis and treatment of uncommon cancer variants in the era of personalized medicine. The EWSR1-ATF1 translocation induces pathological c-Met activation, and so, following unsuccessful CTLA4 and PD-1 blockade immunotherapy, the child received cabozantinib, a small molecule tyrosine kinase inhibitor, with the intent to block c-Met oncogenic effect. In parallel, active immunization, using hapten di-nitrophenyl modified autologous tumor cells was administered with monotherapy PD-1 inhibitor nivolumab. Under this “triplet” therapy, the patient attained an initial partial response and was progression-free for 2 years, in good performance status and resumed schooling. Based on our observation, cabozantinib can be used as an effective and potentially life-prolonging treatment in CCS. We suggest that priming the child’s immune system using her autologous tumor and combating T cell exhaustion with PD-1 blockade may have synergized with the targeted therapy. Combining targeted and immunotherapy is a rapidly growing practice in solid tumors and provides a glimpse of hope in situations that previously lacked any treatment option.

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“…Other clinical results support targeting VEGFR in this tumor, including a trial of the multikinase inhibitor sunitinib which demonstrated five partial responses (PR) in 9 patients with metastatic ASPS in the context of a compassionate use program ( 9 ). In addition, retrospective ( 10 ) and prospective ( 11, 12 ) studies of sunitinib, alone or in combination, indicate that this agent may have clinical activity in several sarcomas, including soft-tissue sarcomas. Therefore, we conducted a phase II randomized trial of single-agent cediranib or sunitinib to determine whether sunitinib or cediranib could be associated with a modestly high rate of clinical response in patients with ASPS.…”

Section: Introductionmentioning

confidence: 99%

Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma

Nguyen

Takebe

Kummar

et al. 2022

Clinical Cancer Research

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Purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few treatment options. We designed a phase 2 randomized trial to determine the activity and tolerability of single-agent cediranib or sunitinib in patients with advanced metastatic ASPS. Methods: Patients 16 years of age and older were randomized to receive cediranib (30 mg) or sunitinib (37.5 mg) in 28-day cycles. Patients could crossover to the other treatment arm at disease progression. The primary endpoint was to measure the objective response rate (ORR) for each agent. Median progression-free survival (mPFS) for the 2 arms was also determined.< Results: Twenty-nine of 34 enrolled patients were evaluable for response. One patient on each of the initial 2 treatment arms had a partial response (ORR: 6.7% and 7.1% for cediranib and sunitinib, respectively). Twenty-four patients had a best response of stable disease (86.7% and 78.6% for cediranib and sunitinib, respectively). There were no significant differences in mPFS for the 2 treatment arms. Clinical benefit (i.e., objective response or stable disease for a minimum of 4 or 6 cycles of therapy) on the first-line tyrosine kinase inhibitor (TKI) therapy did not predict benefit on the second-line TKI. Both drugs were well tolerated. As of August 2021, 1 patient (unevaluable for ORR) remains on study. Conclusion: The study did not meet its endpoints for ORR. Although both TKIs provided clinical benefit, the outcomes may have been attenuated in patients who had progressed ≤6 months before enrollment, potentially accounting for the low response rates.

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Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network

Cited by 16 publications

References 19 publications

A Clear Cell Sarcoma Case: A Diagnostic and Treatment Challenge, with a Promising Response to Trabectedin

A Clear Cell Sarcoma Case: A Diagnostic and Treatment Challenge, with a Promising Response to Trabectedin

Case report: Robust response of metastatic clear cell sarcoma treated with cabozantinib and immunotherapy

Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma

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