Brief Guide to Current Treatments for Metastatic Lung Cancer

Mark G. Kris, MD


July 23, 2018

Hello. This is Mark Kris from Memorial Sloan Kettering in New York City, speaking today about the current flurry of information and discussion about the best treatments for lung cancers at the time of diagnosis. Today I am going to focus on patients with metastatic spread, for whom systemic therapy will be the core of their treatment program.

The explosion of information and clinical trial data, and the explosion of opinions and talking heads—like me—must be dizzying to the people who have to make these treatment decisions today. As the amount of data and information has grown and become more diverse, the truth is that the decision-making is actually in some ways much simpler now. In my mind, [the decision] boils down to this: When you find a target for treatment, you treat patients with the targeted therapy first. When there is no target, the standard of care would be a platinum-containing chemotherapy regimen and, for today, an immune checkpoint blocker; the one that's available and approved with chemotherapy is pembrolizumab.

Let's first talk about the targeted therapies. We have available treatments that target EGFR, ALK, and ROS1 mutations. We also have treatments in compendia for BRAF, HER2, and for MET exon 14 mutations.[1,2] When any of the those targets are found, patients should be treated with a targeted therapy. Moreover, there are additional targets now available that help us choose immune therapies. The first would be tumor mutational burden (TMB).

I believe that there is very good evidence that if patients have high TMB—which generally [does not correlate] with PD-L1—patients should receive immune treatment upfront.[2,3] The approach that has been the most tested and for which clinical trial data are available is the combination of ipilimumab and nivolumab.[3] I understand that [this is not yet approved] by the US FDA and there could be some pushback from payers, but that is where the data are today.

For patients with a high PD-L1 (greater than 50%), or for patients with microsatellite instability—again, a very rare condition in lung cancers—those folks should receive an immune checkpoint blocker such as pembrolizumab, although I believe that there is some consensus that any of the immune checkpoint blockers would be a good choice in that setting.[4]

If you do not have a gene target, high TMB, or high PD-L1, the treatment of choice would be a platinum-based chemotherapy with an immune checkpoint blocker. The one with the greatest amount of data and formal approvals as of today would be pembrolizumab.[5] If you have adenocarcinoma, the treatment would be pemetrexed, ideally cisplatin and pembrolizumab. If you have a squamous cell carcinoma, the best treatment would be albumin-bound paclitaxel with cisplatin and pembrolizumab. For small cell, the treatment would be cisplatin or carboplatin-etoposide and likely pembrolizumab.

If you look at all of the data, I believe that these are the treatments with the greatest degree of consensus. I understand that there are not clear approvals for some of these treatments in the small cell lung cancer area—for example, the combination of ipilimumab and nivolumab for patients with high TMB—but that is where the data are. I believe the field will be moving there.

[These developments] bring to mind the absolute need for comprehensive upfront testing. To treat our patients best in 2018, we need a complete interrogation of their tumors when the diagnosis of lung cancer is first suspected.

Please work with your colleagues who obtain these initial biopsies. Make sure there is enough tissue for an adequate estimation of the cell type because you need that to choose chemotherapy, which will be the choice for most patients. You need sufficient information to conduct immunohistochemistry studies to look for PD-L1, among other things, and also, of course, to find gene targets as well; and you need comprehensive profiling both for the gene targets and TMB.

Now is a fantastic time; we have so many more treatment choices. We can more precisely choose therapies with better results and better tolerability. Things are changing, and they are clearly changing for the better. It's more work for oncologists but so much better for our patients.


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