A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

Wilky, Breelyn A.; Trucco, Matteo; Kolonias, Despina; Wieder, Eric; Subhawong, Ty K.; Rosenberg, Andrew E.; Kwon, Deukwoo; Park, Wungki; Florou, Vaia; Kerr, Darcy A.; Sfakianaki, Efrosyni; Merchan, Jaime R.; Komanduri, Krishna V.; Trent, Jonathan C.

doi:10.1200/jco.2018.36.15_suppl.11547

Cited by 10 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients with alveolar soft part sarcoma, the PFS rate at 3 months was 90.9%, and the best objective response rate was 45.5%. This combination treatment is tolerated well with promising activity in alveolar STS 44. One study revealed the deletion mutation of a mismatch repair (MMR) gene that might be one cause of the good clinical efficacy of PD-1 blockade in alveolar soft part sarcoma 45…”

Section: Pd-1 Blockade Combined With Other Agents For the Treatment Omentioning

confidence: 99%

<p>Recent advances and application of PD-1 blockade in sarcoma</p>

Zuo

Zhao

2019

OTT

View full text Add to dashboard Cite

The role of the programmed death-1 (PD-1) signaling pathway in tumor immunotherapy is becoming increasingly important, and several PD-1-blocking agents have been approved by the US Food and Drug Administration. PD-1-blocking therapy alone or in combination with other therapeutic modalities has become a standard treatment for several kinds of solid tumors. However, sarcomas are not indications for anti-PD-1 therapy. Sarcomas are a group of heterogeneous diseases that can currently only be cured by surgery at the early stage. No effective treatments exist for sarcoma patients in advanced stages. Owning to the diversity of sarcomas, it is very difficult to conduct randomized controlled clinical studies on specific subtypes of sarcomas. Although clinical studies of sarcomas continue, few breakthroughs in the treatment of sarcomas have been achieved over the past decades. This review summarizes recent progress in anti-PD-1 therapy for sarcomas. Based on the published data, PD-1 blockade may be more effective in combination with other modalities for the treatment of sarcomas. In addition, biomarkers may be used to ascertain sensitivity to PD-1 blockade in sarcoma patients.

show abstract

Section: Pd-1 Blockade Combined With Other Agents For the Treatment Omentioning

confidence: 99%

<p>Recent advances and application of PD-1 blockade in sarcoma</p>

Zuo

Zhao

2019

OTT

View full text Add to dashboard Cite

show abstract

“…In 30 evaluable patients that included ASPS, UPS, LMS, and other histologies, the overall ORR was 21.9%. Interestingly, ASPS histology have the highest ORR at 45% (127). Other studies also have suggested that ASPS may be more susceptible to ICI because of a genomic mismatch repair deficiency mutation signature (128), which is associated with a higher response to ICI in other cancer types (129).…”

Section: Modulation Of the Tumor Microenvironment To Improve Response To Immunotherapymentioning

confidence: 95%

Next frontiers in systemic therapy for soft tissue sarcoma

Yen

Chen

2018

Chin. Clin. Oncol.

View full text Add to dashboard Cite

Soft tissue sarcoma (STS) is a heterogeneous disease with more than 50 subtypes. Once the disease reached locally advanced or metastatic status, the standard treatment remains to be chemotherapy. Current understanding of the underlying molecular and genomic mechanisms of different histology subtypes have led to encouraging development of new drugs in treating STS. Besides molecular targeted therapy, immunotherapy have also shown promising advancement in solid tumor treatments. This review will be in two parts. The first part will focus on the molecular targeted agents aiming at molecular or genetic alterations that are more specific in STS, including antiangiogenic molecules, plate-derived growth factor receptor alpha (PDGFRA) monoclonal antibody, colony-stimulating factor-1 receptor (CSF-1R), selective inhibitors of nuclear export (SINE), cyclin-dependent kinase 4/6 (CDK 4/6), mdm2, and epigenetic regulators. We also discussed in depth about how current precision medicine influences the treatment paradigm in STS. In the second part, we focus on the landscape of immunotherapy in STS including immune checkpoint inhibitors (ICIs) and the combinations of immunotherapies or with other molecules that could modulate the tumor microenvironment. These included the program cell death-1 receptor and its ligand (PD-1/PD-L1), cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the combination with anti-angiogenic agents that could facilitate the trafficking of T cells. Strategies targeting the tumor-associated antigen NY-ESO-1, which is commonly observed in synovial sarcoma and myxoid round cell liposarcoma, via viral vaccines and adoptive T cells will also be discussed. These new frontiers of treatment that are developed with better insights into sarcoma and immune biology hopefully will change the treatment paradigm of advanced STS in the future.

show abstract

“…Combination immune checkpoint strategies continue to be evaluated in multiple histology-specific phase I/II studies. In data presented at the 2018 ASCO annual meeting, pembrolizumab combined with axitinib, a small molecule inhibitor targeting VEGFR, c-KIT, and PDGFR, demonstrated promising activity in STS, particularly in ASPS, where an ORR of 45% was reported with preliminary evidence of durable responses 58 . Case reports and small case series have additionally supported the concept of checkpoint inhibition in ASPS 59 , 60 .…”

Section: Immunotherapymentioning

confidence: 99%

Making progress in a rare disease: emerging therapeutics in soft tissue sarcomas

Choe

Riedel

2018

F1000Res

View full text Add to dashboard Cite

Sarcomas are rare tumors derived from mesenchymal connective tissues in the body. Because there are well over 50 histologic sarcoma subtypes, including malignant and non-malignant pathologies, clinical courses and therapeutic management are widely divergent. In general, therapeutic options across all soft tissue sarcomas are limited in number and are often generalized across multiple sarcoma histologies. The recent emergence of molecularly targeted therapies and immune-based agents presents a future of refined systemic treatment practices that are rationally tailored to the tumor by histologic subtype and biologic mechanisms.

show abstract

A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

Cited by 10 publications

References 0 publications

<p>Recent advances and application of PD-1 blockade in sarcoma</p>

<p>Recent advances and application of PD-1 blockade in sarcoma</p>

Next frontiers in systemic therapy for soft tissue sarcoma

Making progress in a rare disease: emerging therapeutics in soft tissue sarcomas

Contact Info

Product

Resources

About