NGS Reveals Lung Cancer Actionable Mutations in Small Transbronchial Specimens

Actionable mutations can be detected in small lung cancer biopsy samples using next-generation sequencing

medwireNews: Amplicon-based next-generation sequencing (NGS) could be used to guide molecularly targeted treatment decisions in patients with lung cancer using a single, small transbronchial biopsy specimen, suggest research published in the Annals of Oncology.

Kazuto Nishio, from Kinki University in Osaka, Japan, and co-authors report that the small tumour samples showed potentially actionable genetic alterations in 44 of 110 patients. Such mutations were detected in 50% of the patients with adenocarcinoma and 14% of those with squamous cell carcinoma, although no such mutations were identified in small-cell lung cancer patients.

In all, 62% of 37 patients with advanced or recurrent lung cancer who had an actionable mutation were treated with a matched molecular therapy, including 95% of the 19 patients with an EGFR mutation and 25% of those with a KRAS mutation. However, none of the three patients with PIK3CA mutations were given targeted therapy.

And patients with an actionable mutation who received targeted therapy had significantly longer overall survival (OS) than both those who did not have such a mutation and patients with an actionable change who were not given targeted therapy, with median OS unreached versus 18.1 and 6.1 months, respectively. The corresponding hazard ratios were 0.44 and 0.14.

The researchers explain that multiplex genomic testing was performed on small single formalin-fixed, paraffin-embedded biopsy samples, largely obtained using transbronchial biopsy, with a success rate of over 95%.

The panel screened for mutation hotspots in 22 genes associated with lung and colon cancer, plus 72 variants of ALK, RET, ROS1 and NTRK1 fusion transcripts, although the researchers observe that the availability of drugs in the Japanese population meant the study “essentially compared outcomes between patients with or without EGFR, ALK, ROS1, or RET alterations.”

“Moreover”, they caution, “it remains unclear whether targeted treatment of patients positive for actionable changes other than EGFR mutations or ALK rearrangement showed an efficacy similar to that for treatment of patients positive for EGFR or ALK alterations with corresponding tyrosine kinase inhibitors.”

Nevertheless, the team concludes: “We have demonstrated the successful application of the amplicon-based NGS approach to the performance of multiple genomic tests with a single small [formalin-fixed, paraffin-embedded] tumor specimen obtained by transbronchial lung biopsy.

“Such multiplex genomic testing will assist physicians in matching patients found to harbor actionable mutations with available targeted treatments or clinical trials of new targeted agents.”


Takeda M, Sakai K, Terashima M, et al. Clinical application of amplicon-based next-generation sequencing to therapeutic decision-making in lung cancer. Ann Oncol 2015; Advance online publication 29 September. doi: 10.1093/annonc/mdv475

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