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Larger NGS Gene Panel Linked to More Clinical Utility

Evaluation of the clinical utility of two different size next-generation sequencing gene panels in solid tumours showed a preference for a larger panel across all tumour types investigated
16 Oct 2020
Personalised medicine

Comparison of two next-generation sequencing (NGS) panels showed that the larger number of actionable gene sites contained in the FoundationOne Panel® (Panel 315) provided increased actionability by targeted therapies information across several tumour types that may aid in guiding clinicians, investigators reported in a poster presented at the MAP 2020 Virtual Congress.

According to Berna Özdemir, Oncology, CHUV - Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, currently there are no data to guide the selection of NGS gene panels for clinicians, which prompted Dr Özdemir and colleagues to evaluate NGS gene panels. The investigators compared two commercially available NGS gene panels of different size for clinical utility by quantifying the number of detectable actionable alterations in various solid tumour types identified in a systematic review of the literature.

The investigators evaluated the Ion AmpliSeq Cancer Hotspot Panel® (Panel 50), which covers the hotspots of in 50 genes and the FoundationOne Panel® (Panel 315) covering the complete exons of 315 genes.

The targeted therapies included FDA approved drugs as well as experimental agents

The investigators were able to classify 86% of the genes in the Panel 50 versus 50.3% of the genes in the Panel 315 as clinically actionable.

They matched targeted therapies that could be proposed based on the results from the Panel 50 or Panel 315 using 145 compounds; of these, 99 had received the US Food and Drug Administration (FDA) approval, 14 had been tested in active phase I/II trials, 21 in phase II trails, one compound in a phase II/III trial, and 10 agents had been evaluated in phase III clinical trials. They were respectively categorised as FDA-approved drugs with on-label or off-label use, and as experimental molecules. Putative targeted therapies using the Panel 50 and Panel 315 were identified for 42% versus 18.9% for FDA on-label drugs, 10% versus 6.9% of FDA off-label drugs, and 34.0% versus 24.3% for experimental molecules, with the respective panels.

Across tumour types, the Panel 315 consistently matched more actionable sites to existing agents

Regarding solid tumours, the number of actionable alterations across diverse tumour types was a median 50% higher using the Panel 315 compared to the Panel 50 (T-test, p = 1.72 x 10-5).

This gain was possibly due to Panel 315 containing a higher number of genes involved with homologous recombination repair deficiency that could be targeted by PARP inhibitors (21 genes versus one gene in Panel 50) and also containing 8 genes associated with microsatellite instability compared to one gene in Panel 50 that, therefore, could be targeted by immune checkpoint inhibitors.

Specifically, in lung tumours, with Panel 50 actionability was 29.8% compared to 54.4% with Panel 315, thus a 45.2% increase in actionability was provided by Panel 315.

Across other tumour types, the increase in actionability with the Panel 315 was 50% in glioblastoma, 37.0% in melanoma, 45.0% in sarcoma, and 48.4% in head and neck squamous cell carcinoma. An increase in actionability with the Panel 315 was also observed for ovarian (50%), prostate (60%), cervical (72%), pancreatic (61.1%), colorectal, (43.5%), gastric (55.6%), and breast (50.0%) cancers.

Conclusions

Based on these findings, the authors found that the larger gene panel provided a substantial gain in actionability with either FDA approved or experimental drugs. They attribute this gain to Panel 315 containing a higher number of genes related to homologous recombination repair deficiency that could be targeted by PARP inhibitors and also containing 8 genes associated with microsatellite instability that could be targeted by immune checkpoint inhibitors.

No external funding was disclosed.

Reference

7P - Özdemir B, M. Charrier, C.L. Gerard, et al. Comparison of the clinical utility of two different size next generation sequencing (NGS) gene panels for solid tumours. MAP 2020 Virtual Congress (9-10 October 2020).

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