The Changing Landscape of Treatment for EGFR+ Lung Cancer - Episode 4

Managing Disease Progression in EGFR+ NSCLC


Sai-Hong Ignatius Ou, MD, PhD: One of the changing paradigms in the treatment of EGFR-mutant lung cancer is that there is increasing frequency by the clinical investigator to rebiopsy at disease progression because of different resistance mechanisms that we know about. Preferably, we like to use a tumor-based biopsy because we can detect the small cell transformation and possibly detect the MET and RET fusions, the receptor tyrosine kinase fusions, more accurately. With the tumor-based biopsy, you know you can always get to the resistance mechanism. The disadvantage of a liquid biopsy is that not all of the tumors are shed into the blood. You may not be able to detect the resistance mutation.

The advantage of a liquid biopsy is that it collects all of the disease sites in the body. It’s an aggregate of what is happening in the body. With the tissue-based biopsy, or the tumor-based biopsy, you only biopsy the site that is progressing. If there is another site in the body that is progressing, it may be a different mechanism and you may not be able to detect it. So, they both have advantages and disadvantages.

Ideally, a liquid biopsy is probably the preferable choice to do because it’s easy. It’s just a blood draw, and with the currently commercially available liquid biopsy in the United States, most of the resistance mechanisms can be detected, with the exception of small cell transformations, where you really need a tissue-based diagnosis. If you pick up TP53 mutations in a liquid biopsy, if they are looked for, that’s also a good indication of a small cell transformation.

Going forward, since we are now starting everybody on osimertinib as frontline treatment of EGFR-mutant non—small cell lung cancer, on disease progression, I prefer to biopsy the tissue. If it’s easily accessible and it’s not high-risk to the patient, I like to biopsy the actual tissue, but it’s so easy to draw blood that I will almost always do a liquid biopsy. In most cases, if I can detect a resistance mechanism that has been published, that may be sufficient enough for me to tailor the subsequent treatment based on whether a resistance mechanism is seen or not.

For example, if I see a MET amplification, I may consider adding crizotinib to osimertinib. Crizotinib is a very strong MET inhibitor. If I don’t see any of these resistance mutations that I mentioned before, then I tend to use chemotherapy. Whether I continue osimertinib or not depends on the patient. In most cases, I like to continue osimertinib and add chemotherapy—carboplatin and pemetrexed—because I like to continue to suppress the emergence of CNS [central nervous system] metastasis, where I think osimertinib is very useful.

In some cases, I would just stop osimertinib and continue with chemotherapy, a few cycles, to reduce the tumor burden. And then, at the maximum chemotherapy response, I would add back osimertinib.

Transcript Edited for Clarity