It depends on the disease, the lab, the resources available, the throughput in the laboratory, the turnaround time requirements, and cost consider- ations,” he said. “It is cheaper, more rapid, more economical than the more comprehensive approaches, and in some ways more clinically suited.”Īt the same time, Berger said the choice of NGS strategy depends on clinical and practical factors. “There is a sweet spot in the middle, and this has been our approach,” he said, referring to MSK-IMPACT. At one end of the spectrum, hotspot panel testing is a lower-cost option that offers a fast turnaround, while at the other end, whole exome sequencing provides the greatest potential for discovery. In describing the current landscape for NGS testing, Berger said there are 3 main test categories: hotspot panel, with amplicon capture of approximately 10 to 50 genes cancer gene panel, with hybridization capture of about 100 to 500 genes and whole exome sequencing, with hybridization capture of approximately 20,000 genes.
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The FDA is currently considering a supplemental biologics license application for the combination of nivolumab (Opdivo) plus low-dose ipilimumab (Yervoy) for the frontline treatment of patients with advanced NSCLC with TMB ≥10 mutations per megabase.Īlthough dMMR/MSI is “very rare in lung cancer,” Berger says patients with this signature may be candidates for pem- brolizumab (Keytruda), a PD-1 inhibitor that is approved for patients with unresectable or metastatic MSI-high or dMMR solid tumors who have progressed following prior treatment and who have no satisfactory alternative treatment options.
TMB is being explored as a biomarker in NSCLC. “The broad testing allows us to capture not just the common but also the rare mutations, and it also gives us information about more complex mutational signatures that are increasingly important for predicting response to immunotherapy,” Berger said. Larotrectinib (Vitrakvi), a selective tyrosine receptor kinase (TRK) inhibitor, and entrectinib (RXDX-101), an oral pan-TRK inhibitor, are among the drugs being developed in this space. He cited the example of NTRKfusions, which have been identified in less than 3% of NSCLC cases. In NSCLC, such testing is growing increasingly relevant, notably because of novel therapies being developed for less prevalent gene fusions, Berger said in an interview with Targeted Therapies in Oncology. He added that some patients with earlier-stage cancers may also undergo testing if they are treated through surgical oncology. MSK now seeks to offer NGS testing to patients with meta- static cancer across all solid tumor types, particularly those with NSCLC, Berger said.
In NSCLC, the same combination gained FDA approval in 2017 for patients with metastatic disease that harbors BRAFV600E mutations, which are found in 1% to 2% of lung adenocaricnomas. “What might have been done in the context of an individual tumor type for a small core set of genes or mutations has now expanded to all different cancer-associated genes, knowing that mutations that may be more commonly observed in one cancer may also be less frequently observed in other cancers but also can provide informed treatment decisions for those patients,” said Berger.Īs an example, he cited BRAFmutations, which have been observed in approximately 50% of melanomas and have prompted the development of dual pathwaytargeting agents, including the combination of dabrafenib (Tafinlar) and trametinib (Mekinist). 1The assay also evaluates tumor mutational burden (TMB) and mismatch repair deficiency (dMMR) or microsatellite instability (MSI). The center developed the MSK-IMPACT (integrated mutation profiling of actionable cancer targets) comprehensive panel for sequencing 468 cancer-associated genes. Kravis Center for Molecular Oncology during a presentation at the 13th Annual New York Lung Cancers Symposium hosted by Physicians’ Education Resource ®, LLC. Berger, PhD, described the NGS landscape through the lens of his experience as the associate director of the Marie-Josée and Henry R.
Increasing clinical relevance of less common gene signatures and alterations is leading to a benefit from broad-panel next-generation sequencing (NGS) testing for patients with metastatic nonsmall cell lung cancer (NSCLC), according to an expert at Memorial Sloan Kettering (MSK) Cancer Center.
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