Next-Gen Sequencing at Diagnosis and as Routine Care for Patients With Lung Cancer

Mark G. Kris, MD


May 01, 2018

Hello. This is Mark Kris from Memorial Sloan Kettering Cancer Center in New York. I would like to speak about the use of next-generation sequencing as part of the routine care for patients with lung cancer.

I think all of us have seen the additional benefits from finding a targeted therapy for patients with lung cancer. The only way we can do this is by testing patients. We now have more access to next-generation sequencing panels, which can provide all of the information we need to select from the different standard therapies available for patients with lung cancer. Clinical trials, of course, are an option as well.

It makes the most sense to do next-generation testing at diagnosis and to make next-generation sequencing a complete testing for all relevant genomic alterations—as part of the initial biopsy.

In 2018, we cannot plan treatment for a person with lung cancer—at almost any stage—without a very thorough pathologic evaluation for cell type, IHC [immunohistochemistry] testing, FISH [fluorescence in situ hybridization] testing, and next-generation testing. The only way we can do this is to obtain an adequate specimen at the time of diagnosis, to make sure the specimen goes to our pathology department, and to request all necessary testing on day 1.

From a very practical standpoint, if the testing starts on day 1, at the time of biopsy, the results will be available, or very quickly available, when the patient has concluded his or her other evaluations and extent of disease evaluation.

From the medical oncologist standpoint, we have to work closely with our colleagues in interventional radiology, pulmonology, and thoracic surgery to ensure that we obtain the specimens, and with our pathology colleagues to make it very clear to them the information we need to best select therapy for patients. We need to know the exact cell type, have immunohistochemistry testing to help confirm cell type, and also obtain PD-L1 testing, FISH testing (when necessary), and next-generation testing.

Two papers have recently been published in the Journal of Clinical Oncology that point to the additional usefulness of next-generation testing in making treatment decisions. The first is a paper by Rizvi et al[1] (not my former partner Naiyer Rizvi, who is now at Columbia, but Hira Rizvi, MD, who is now at Memorial Sloan Kettering Cancer Center). This paper looks at the use of next-generation sequencing from standard testing panels to predict tumor mutational burden—a very potent predictor, and perhaps our best predictor today, of response to immune checkpoint blockade.

In their study, Rizvi et al[1] showed a very close correlation between whole exome sequencing and standard next-generation sequencing to determine tumor mutational burden, as well as the benefit of using that parameter to help predict response.

The second paper is by Hainsworth et al,[2] who reported results from a study called MyPathway, wherein patients with a variety of different cancers had next-generation testing upfront. The authors of this paper showed the presence of an actionable target in a large proportion of patients and also [actionable targets] in many diseases beyond lung cancers. In particular, they discovered amplifications in HER2, for which we have a number of very well-tested and safe agents from our breast cancer colleagues. If you find HER2 amplification, you can then offer HER2-targeted therapies to these patients. For lung cancer patients, at least one, T-DM1, is in the National Comprehensive Cancer Network guidelines right now.

Next-generation testing is important. It is available, and I urge you to do it at diagnosis. I also urge you to work with your colleagues in interventional radiology, thoracic surgery, pulmonology, and pathology to have this testing done in all patients at the time of diagnosis, as this is most efficient. It will give you information to help choose therapy for that patient and a lot more.


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