Transcript Related Guidelines

Biomarker Testing and Treatment for Metastatic NSCLC in Patients Under 40

Sandip Patel, MD · UC San Diego


March 16, 2022

This transcript has been edited for clarity.

Younger patients with metastatic non–small cell lung cancer (NSCLC) are typically under the age of 40. These are patients who most commonly have never smoked or are rare smokers, and we wouldn't normally expect them to develop lung cancer, which is typically a disease of smoking in a more elderly population.

And so, more commonly than not, these patients will have what are called driver mutations.[1] These are mutations that fuel the cancer for which we have targeted therapies that can help block the growth of these cells. The most important point I can make about younger patients with metastatic NSCLC is to make sure that they undergo the standard seven NCCN-recommended biomarker tests.[2]

That said, these are often patients who, even beyond the seven biomarkers (if those are all negative), may benefit from broader-based molecular profiling. In my clinic, that involves next-generation sequencing, often with cell-free DNA-based methods, especially for patients with limited tissue or not easily available tissue, or tumor-based methods, especially if you're looking for some of the novel fusions that are quite rare for patients who may have initially tested negative for the seven NCCN molecular biomarkers.

The reason to do this, rather than giving chemotherapy or immunotherapy, which is not likely to benefit patients with low–tumor mutational burden, driver mutation–type NSCLC and may lead to side effects if one initiates targeted therapy at a later time (such as pneumonitis with EGFR inhibitors), is because you're very likely to find a driver mutation in these patients.[1,3]

In several of the studies that have looked at patients with metastatic NSCLC who are less than 40 years old, about three quarters of these patients had a driver mutation, for which their best therapy is a pill. Whether this is an EGFR-directed therapy, ALK, ROS1, MET exon 14 (skipping or amplified), HER2, BRAF, or some of the more novel fusions that we can now detect, such as n-TRK or RET,[4] this is definitely a patient population where broad-based molecular profiling in particular may lead to improved therapeutic outcomes, in terms of both survival and quality of life. The ability to use a targeted therapy in the most appropriate fashion is the best help for these young patients with metastatic NSCLC.


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