COMMENTARY

Where Do We Stand With Lung Cancer Treatment for 2017?

Mark G. Kris, MD

Disclosures

January 31, 2017

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Hello. This is Mark Kris from Memorial Sloan Kettering Cancer Center, and I would like to speak a little bit about the dramatic changes we have had in the treatment of lung cancers in 2016.

I would like to first focus on the upfront treatment of lung cancers and how it has changed in the past few months. I think the biggest change is emergence of the use of programmed death-ligand 1 (PD-L1) inhibitors, particularly pembrolizumab, as initial therapy in individuals with high levels of expression of PD-L1 protein. By now, you know there was a randomized trial comparing chemotherapy with upfront pembrolizumab, and for people who had PD-L1 expression 50% or greater, those patients had greater rates of shrinkage, greater progression-free survival, and greater overall survival by starting with pembrolizumab.

From a very practical standpoint, particularly for patients with squamous cancer, the first part of their care should be the determination of PD-L1 status. If PD-L1 positive, then go right to pembrolizumab. If PD-L1 negative, then go to one of our standard chemotherapy regimens for squamous cell cancer, and that would be cisplatin and gemcitabine or cisplatin and a taxane. We tend to use docetaxel.

The other drug that is available—and I urge you to consider it in every patient with squamous cancer that has low PD-L1 expression at diagnosis—is adding necitumumab. It is generally a reasonably well-tolerated drug. It does add in terms of benefit for overall survival; it does not add a lot, but it does add. I think for those patients who are willing to accept the additional hassle, the additional side effects, it is a worthy addition, and I think you should at least have it on the table to discuss it with every patient.

What about an adenocarcinoma? Again, once a diagnosis of adenocarcinoma is confirmed, the majority of oncologists today would still recommend looking for a target. EGFR, ALK, ROS1, MET, and BRAF are very valid targets for which there is a targeted therapy, and I would urge that the first step in those cases would be to see whether a target is there. That has changed tremendously too. Most oncologists across the United States now not only have the availability of next-generation panels from tissue testing, but also next-generation panels and focused next-generation panels from blood testing.

The barriers to testing up front are going away. There is not that absolute need for tissue anymore. There is much greater availability, and we need to get the testing done. For most patients, doing the testing and waiting until the results are available makes sense.

What needs to be added to that testing armamentarium is obtaining PD-L1 expression determination from that same tissue. For patients with adenocarcinoma without a driver, PD-L1 testing is important. If it is positive, greater than 50%, we would go to pembrolizumab as the initial treatment. If it is negative, we would go to a standard chemotherapy program, and for me, the standard chemotherapy program would still be pemetrexed. It would be cisplatin if the patient is fit to have it and if the degree of side effects that cisplatin has is appropriate for that patient in that clinical setting.

Finally, the consideration in every patient of bevacizumab: The majority of patients can receive bevacizumab with their standard chemotherapies, and it should be considered. It improved rates of response. It improves progression-free survival and overall survival when given initially with standard chemotherapies, and it is a current standard of care.

For adenocarcinoma and squamous carcinoma, the important thing is to find a target for the adenos. For both types of cancer, the next issue is to do PD-L1 testing. I have to say, by the patients who come to see me in consultation, that this testing is widely available now. It is a rare patient who does not come to me for a consultation who has not had PD-L1 testing done already. It is again a standard immunohistochemistry test; it could generally be easily added to the testing that is done, along with immunohistochemistry testing at the time of the diagnosis of lung cancers.

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