Future Treatment Modalities in Sarcoma: Insights From ASCO 2017

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Targeted and immunotherapeutic approaches are poised to change how sarcoma will be treated in the future. Trials are being used to match tumors with appropriate treatment choices.
Targeted and immunotherapeutic approaches are poised to change how sarcoma will be treated in the future. Trials are being used to match tumors with appropriate treatment choices.

Soft tissue sarcomas (STS) are a heterogeneous group of cancers with over 50 different histologies that arise from distinct tissues. The primary sites for STS are the extremities, trunk, visceral, retroperitoneum, and head and neck.

Many subtypes of STS are also associated with characteristic genetic aberrations, including single base pair substitutions, deletions, amplifications, and translocations.1

Individuals with a good performance status who present with early disease are treated aggressively with neoadjuvant chemotherapy and radiation therapy, according to sarcoma expert Breelyn A. Wilky, MD, of the Sylvester Comprehensive Cancer Center in Miami, Florida.

In patients with widespread disease, she added, treatment is typically undertaken for palliation of symptoms.

At the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, an education session and several presentations addressed the changing treatment landscape for patients with STS.

New Targeted Treatment Approaches

In 2016, the US Food and Drug Administration (FDA) granted accelerated approval for olaratumab, a monoclonal antibody targeting PDGFRα, for the treatment of patients with STS not amenable for curative treatment with radiotherapy or surgery.2

Pazopanib, a multiple tyrosine kinase inhibitor (TKI), also shows single-agent activity in most advanced STS. One study showed that pazopanib significantly improves progression-free survival (PFS) compared with placebo (4.6 months vs 1.6 months; P < .0001).3

Imatinib and sunitinib also show efficacy in advanced and/or metastatic STS.4,5 Crizotinib, an ALK inhibitor, shows activity in inflammatory myofibroblastic tumors with ALK translocations.6

At the 2017 ASCO Annual Meeting, cediranib, an inhibitor of VEGFR, was reported to show significant activity in alveolar soft part sarcoma — another rare malignancy unresponsive to traditional chemotherapy.

In CASPS (Clinicaltrials.gov Identifier: NCT01337401), the largest randomized trial in this disease, best response by 24 weeks was a partial response in 21% of patients receiving cediranib (vs 0% in patients receiving placebo). Median PFS for patients in the cediranib arm was 10.8 months compared with 3.7 months for patients in the placebo arm; 1-year overall survival (OS) was 96% compared with 64.3%, respectively.7

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