Personalizing Care for Patients With Sarcoma

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The landscape of complex genetic mutations in sarcomas seen through next-generation sequence profiling provides a rationale for a study to match patients to the appropriate therapy.
The landscape of complex genetic mutations in sarcomas seen through next-generation sequence profiling provides a rationale for a study to match patients to the appropriate therapy.
The following article features coverage from the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Click here to read more of Cancer Therapy Advisor's conference coverage.

The landscape of complex genetic mutations in sarcomas seen through next-generation sequence (NGS) profiling provides a rationale for a study to match patients to the appropriate therapy, according to data reported at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.1

Antoine Italiano, MD, PhD, of the Institut Bergonié in Bordeaux, France, presented an analysis undertaken for 587 patients with sarcoma.

The researchers analyzed mutational and copy number profiles of tumors in patients with sarcoma; the tumors were sequenced through the Genomics Evidence Neoplasia Information Exchange (GENIE) Consortium, which was set up to identify actionable mutations.

The most frequent histologies were leiomyosarcoma (19%), undifferentiated pleomorphic sarcoma (13%), dedifferentiated liposarcoma (9%), angiosarcoma (7%), and synovial sarcoma (7%).

Seventy-three percent of patients had at least 1 mutation, with the most frequent mutations seen in TP53 (35%), ATRX (9%), RB1 (8%), KMT2D (6%), NF1 (5%), ATM (5%), PI3KCA (5%), ERBB4 (4%), PTEN (4%), and ARID1A (4%).

Of the 86% of patients with copy number alteration in their tumors, amplified genes included MDM2 (20%) CDK4 (17%), and GLI1, MAP2KA, and TERT (3% each), while frequently deleted genes included RB1 (13%), CDKN2A (10%), TP53 (10%), and PTEN (9%).

Importantly, 93% of patients had sarcomas with at least 1 actionable mutation — copy number alteration and/or gene fusion.

The results provide a rationale for designing the MUTLSARC trial, which will match NGS profile to the appropriate therapy for patients with advanced soft-tissue sarcoma.

MULTISARC will be the first phase 3 study that is designed to demonstrate the superiority of an innovative treatment strategy in patients with advanced soft tissue sarcomas, Dr Italiano noted.

Patients will be randomized to the standard therapy arm or the experimental arm. All patients will receive first-line doxorubicin.

Patients in the standard arm will then receive standard of care. Patients in the experimental arm will be provided therapy based on actionable mutation.

RELATED: Pembrolizumab Active in Few Soft Tissue, Bone Sarcoma Subtypes

“This will be the largest, most rigorous precision cancer medicine trial implementing exome sequencing and RNA sequencing,” Dr Italiano concluded.

Read more of Cancer Therapy Advisor's coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by visiting the conference page.

Reference

  1. Italiano A, Khalifa E, Laizet Y, et al. Genetic landscape of soft-tissue sarcomas. Moving toward personalized medicine. J Clin Oncol. 2017;35(suppl; abstr 11002).

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