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Frontline Regimens Explored for EGFR-Mutated NSCLC

*December 2020*

John Heymach, MD, PhD Chair, Department of Thoracic/Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center in a Q&A session:

Targeted Oncology™: How would you reassure a patient who is eager to start treatment?

HEYMACH: Patients are anxious to get their treatment started. I tell them that their tumor has probably been growing for 2 to 3 years, on average; [the only thing] that’s changed in the last 1 or 2 weeks is their knowledge of it. But the tumor has been [growing] for a couple of years, so an extra couple of weeks doesn’t make a difference.

Interestingly, if you start immunotherapy and then go to osimertinib [Tagrisso], the risk of pneumonitis may be dramatically higher. I try to hold off on immunotherapy before starting a TKI [tyrosine kinase inhibitor]. If I absolutely need to start treatment, I start chemotherapy [and] leave the immunotherapy out until we get the results and then switch to immunotherapy or a TKI.

There is a rationale for all of these but if I have to start something because a patient needs something quick, I’ll often start chemotherapy without the immunotherapy and then add it in after the [molecular] profiling [results] come back.

How have the recommendations for frontline testing in nonsquamous NSCLC changed?

The NCCN [National Comprehensive Cancer Network] guidelines are changing so quickly.1 In the last couple of months, we had approval for RET [rearrangement-positive NSCLC] with selpercatinib [Retevmo]. For MET exon 14 [skipping mutations], there is capmatinib [Tabrecta]. Now we have BRAF/MEK inhibitor drugs with dabrafenib [Tafinlar] and trametinib [Mekinist]. We have ROS1 drugs like crizotinib [Xalkori] and entrectinib [Rozlytrek], a host of ALK inhibitors, and multiple EGFR inhibitors.

There are now approved therapies for 7 different driver oncogenes. Based on this, the NCCN recommendations moved to NGS. Read more.