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ONCAlert | Upfront Therapy for mRCC

The Unprecedented Data of Next-Generation Sequencing

Targeted Oncology
Published Online:1:32 PM, Fri February 15, 2019

Mark A. Socinski, MD: Lung cancer, whether it be non–small cell lung cancer, particularly nonsquamous non–small cell lung cancer, should be viewed as a genotypic disease. There are a number of driver mutations in other DNA alterations, such as translocations. Obviously NCCN [National Comprehensive Cancer Network] Guidelines today call out for testing all of those patients for EGFR and BRAF mutations, as well as for ALK and ROS1 translocations. And I would argue that you should go beyond that and things such as MET, exon 14 skip mutations, RET fusions, HER2 alterations, and those sorts of things should be part of a broad comprehensive molecular testing in stage IV disease.

I think with regard to the tumor mutation burden and microsatellite instability, I think the data [are] still a little early in terms of really solidifying it for routine clinical use today in making clinical decisions. But we had some encouraging data with regard to tumor mutation burden in lung cancer from the results of CheckMate 227. Most of that was based on subset data. It was based on progression-free survival outcomes. We had a subsequent press release looking at overall survival where a tumor mutation burden didn’t seem to be helpful in predicting benefit from checkpoint inhibition. So I still think it’s a little early in routine clinical practice to be using tumor mutation burden.

The rate of microsatellite instability is very low in non–small cell lung cancer. We’re talking about 1% or so. So I don’t know that will have a lot of clinical utility in non–small cell lung like it may have in other cancers. But I think the important message is, to all oncologists dealing with lung cancer patients, particularly non–small cell, nonsquamous patients, that all of those patients must undergo comprehensive molecular testing. I would favor next-gen sequencing where you look at all the potential targets. In my opinion, there are 8 or 9 targets today that will affect what you may do with that patient and can really change the course of the, of the patient’s disease if you identify one of those molecular alterations where you can treat it with a targeted therapy.

Transcript edited for clarity.

Mark A. Socinski, MD: Lung cancer, whether it be non–small cell lung cancer, particularly nonsquamous non–small cell lung cancer, should be viewed as a genotypic disease. There are a number of driver mutations in other DNA alterations, such as translocations. Obviously NCCN [National Comprehensive Cancer Network] Guidelines today call out for testing all of those patients for EGFR and BRAF mutations, as well as for ALK and ROS1 translocations. And I would argue that you should go beyond that and things such as MET, exon 14 skip mutations, RET fusions, HER2 alterations, and those sorts of things should be part of a broad comprehensive molecular testing in stage IV disease.

I think with regard to the tumor mutation burden and microsatellite instability, I think the data [are] still a little early in terms of really solidifying it for routine clinical use today in making clinical decisions. But we had some encouraging data with regard to tumor mutation burden in lung cancer from the results of CheckMate 227. Most of that was based on subset data. It was based on progression-free survival outcomes. We had a subsequent press release looking at overall survival where a tumor mutation burden didn’t seem to be helpful in predicting benefit from checkpoint inhibition. So I still think it’s a little early in routine clinical practice to be using tumor mutation burden.

The rate of microsatellite instability is very low in non–small cell lung cancer. We’re talking about 1% or so. So I don’t know that will have a lot of clinical utility in non–small cell lung like it may have in other cancers. But I think the important message is, to all oncologists dealing with lung cancer patients, particularly non–small cell, nonsquamous patients, that all of those patients must undergo comprehensive molecular testing. I would favor next-gen sequencing where you look at all the potential targets. In my opinion, there are 8 or 9 targets today that will affect what you may do with that patient and can really change the course of the, of the patient’s disease if you identify one of those molecular alterations where you can treat it with a targeted therapy.

Transcript edited for clarity.
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