Targeting NSCLC with Uncommon EGFR Mutations - Episode 2
Insight on EGFR-mutated non–small cell lung cancer’s impact on treatment options and overall patient prognoses.
Sandip P. Patel, MD: EGFR-mutated non–small cell lung cancer is the most common actionable driver that we have in terms of [giving] targeted therapy but not giving immunotherapy, in the sense that immunotherapy tends not to work as well for these patients. It potentiates future toxicity if you introduce targeted therapy in terms of pneumonitis risk. But it’s important to give not only a street name but also the actual address, and that’s similar for EGFR. It’s not enough to say that you live on Main Street, so to speak. What’s the actual address?
Canonical EGFR mutations, such as exon 19 or L858R, represent about 85% of these mutations and are amenable to small-molecule target inhibitors, such as osimertinib. However, exon 20 insertion mutations [are in] 5% to 7% of patients. Even though it’s with an EGFR, the treatments are very different. Osimertinib doesn’t work in that context, and amivantamab or mobocertinib would be your treatment options. When we’re testing, it’s important to test the entirety of the EGFR gene. If you’re doing next-generation sequencing, you’re doing that whether it’s a tissue or a liquid. But it’s important to understand that just saying someone has an EGFR mutation is like saying someone lives on Main Street. You’ve to find a specific address because the therapeutic complications or implications can be profound.
For patients with metastatic EGFR-mutated non–small cell lung cancer with a canonical mutation, such as exon 19 or L858R, the median overall survival is over 3 years. That’s why it’s so important to manage toxicities, whether we’re talking about avoiding whole-brain radiation, doing more stereotactic approaches, or relying on the small-molecule inhibitor for a subset of patients. In terms of the toxicities when adding agents, the median time you’re on the pill is measured in years, with the balance of the benefit and the adverse effects. We’re trying to personalize medicine, in terms of not only the genomics but also the toxicities. If a patient lives 3 hours away, adding an IV [intravenous] infusion would be a last resort. These are the things we think about. We need to think about them when we’re taking care of the patient holistically.
The future is bright for utilizing novel diagnostic tools to help guide patients in terms of their potential risk-benefit from adding additional therapies as we move forward to the small-molecule inhibitors, which represent the standard of care for the treatment of these patients.
Transcript edited for clarity.