A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma

Abstract

Lessons Learned. Pazopanib shows a modest efficacy in metastatic alveolar soft part sarcoma.Clinical outcomes were comparable to those in previous studies using antiangiogenic drugs.Further prospective studies evaluating the benefit of pazopanib in alveolar soft part sarcoma with a larger sample are warranted to validate results.Background.Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignant tumor characterized by an unbalanced translocation, t(X;17)(p11.2;q25), which leads to the fusion of ASPSCR1 to the TFE3 transcription factor. Because this results in the upregulation of angiogenesis‐related transcripts, antiangiogenic drugs have been used in ASPS patients.Methods.This open‐label, single‐arm, multicenter, investigator‐initiated phase II trial was designed to evaluate efficacy and safety of pazopanib 800 mg once daily in patients with metastatic ASPS. The primary endpoint was investigator‐assessed overall response rate (ORR), and secondary endpoints were toxicity, progression‐free survival (PFS), and overall survival (OS). 68Ga‐RGD (Arg‐Gly‐Asp) positron emission tomography (PET) scan and gene expression profiling using NanoString platform were performed for biomarker analysis.Results.Six patients with histologically confirmed metastatic ASPS were enrolled between December 2013 and November 2014. Among six patients, one achieved a partial response (PR) (ORR 16.7%) and five patients showed stable disease (SD). With a median follow‐up of 33 months (range 18.7–39.3 months), median PFS was 5.5 months (95% confidence interval [CI] 3.4–7.6 months), and median OS was not reached. There were no severe toxicities except one patient with grade 3 diarrhea.Conclusion.Pazopanib showed modest antitumor activity with manageable toxicities for patients with metastatic ASPS.

Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study

“…After the initiation of this study, some prospective and retrospective reports on the effectiveness of pazopanib in ASPS were published. Kim et al reported a phase II trial of pazopanib in patients with metastatic ASPS 27 . Six patients were enrolled in the study, with 1 patient achieving PR, and 5 patients showing SD according to RECIST (response rate 16.7%).…”

Precision Medicine in Soft Tissue Sarcoma Treatment

“…Pazopanib, the phase 3 trial of which was discussed above in Section 3, is a TKI that inhibits VEGF receptors as well as other growth factors, and there are retrospective clinical reports that suggested pazopanib treatment resulted in relatively higher response rates in vascular-abundant VEGF-expressing sarcomas compared to other histological subtypes [48]. Patients with an alveolar soft part sarcoma (ASPS), characterized by translocation t(X;17)(p11.2;q25) and known as a vascular-rich tumor, showed high responses to VEGF-targeted therapies in prospective trials, including trials of pazopanib [49][50][51].…”

Activity and Safety of Geptanolimab (GB226) for Patients with Unresectable, Recurrent, or Metastatic Alveolar Soft Part Sarcoma: A Phase II, Single-arm Study

“…[10] However, disease progression commonly developed with VEGFR-TKI treatment and demonstrated a median progression-free survival (PFS) of [13][14][15][16][17][18][19] months with sunitinib, 5.5-13.6 months with pazopanib and 10.1 months with cediranib. [7,[9][10][11][12][13] Immune checkpoint inhibitors (ICIs) represented encouraging effects in ASPS patients. [14][15][16] Groisberg R et al reported two of four patients, diagnosed with ASPS and enrolled in immunotherapy trials, who achieved a partial response (PR) lasting 8 and 12 months after previous 2-4 lines of treatment failure.…”