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Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database
Roberto Carmagnani Pestana1, César Serrano2,3
1Hospital Israelita Albert Einstein, São Paulo, Brazil.
Background:
The development of novel therapies for patients with sarcoma is challenging due to the rarity and diversity of these mesenchymal neoplasms. Hence, histology-agnostic approvals can be of particular interest for the treatment of patients with soft tissue and bone sarcoma.
Methods:
We queried the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database Cohort v12.0-Public to investigate the prevalence of currently Food and Drug Administration (FDA)-approved and other potentially actionable histology-agnostic alterations in patients with soft tissue and bone sarcoma. Targets were identified by a literature review by the authors. Results are presented for each cohort identified in the GENIE database, namely: (1) soft tissue sarcoma (STS), (2) gastrointestinal stromal tumor (GIST), (3) bone sarcoma, (4) uterine sarcoma, and (5) breast sarcoma.
Results:
We identified 7,512 samples of 6,955 patients with sarcoma in the AAACR GENIE database v12.0-Public. Molecular alterations that could lead to the clinical use of a currently approved histology-agnostic therapy were identified in 2.1% of sarcomas (2.6% STS, 1.3% GIST, 1.4% bone, 2.7% uterine, and 0% breast). In addition, 2.9% of patients could be eligible for future histology-agnostic approvals. These specific mutations, fusions, and amplifications occurred in multiple histotypes in all cohorts.
Discussion:
Exploring a public large-scale genomic database, we identified that 5% of patients with sarcoma could be eligible for current histology-agnostic FDA-approved drugs or future potential histology-agnostic indications. These actionable alterations were present in a wide variety of histologies in soft tissue and bone sarcomas, highlighting that next-generation sequencing can be considered for patients with advanced sarcoma to guide treatment strategies.
Insights
Five percent of sarcoma patients may benefit from current or future histology-agnostic therapies. Actionable molecular alterations were found across various sarcoma types, suggesting next-generation sequencing can guide treatment for advanced disease.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Sarcoma treatment is challenging due to rarity and diversity.
- Histology-agnostic therapies offer potential for soft tissue and bone sarcomas.
Purpose of the Study:
- To investigate the prevalence of actionable histology-agnostic alterations in sarcoma patients.
- To identify patients eligible for current or future histology-agnostic drug approvals.
Main Methods:
- Utilized the American Association for Cancer Research (AACR) Project GENIE database (v12.0-Public).
- Analyzed 7,512 sarcoma samples from 6,955 patients.
- Identified actionable molecular alterations through literature review and database querying.
Main Results:
- Actionable alterations for current FDA-approved histology-agnostic therapies were found in 2.1% of sarcomas.
- An additional 2.9% of patients were identified as potentially eligible for future histology-agnostic approvals.
- Actionable alterations were identified across multiple sarcoma histotypes, including soft tissue, bone, and uterine sarcomas.
Conclusions:
- Approximately 5% of sarcoma patients may be eligible for current or future histology-agnostic treatments.
- Actionable alterations are present in diverse sarcoma histologies.
- Next-generation sequencing is recommended for advanced sarcoma patients to guide treatment decisions.
