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The Current Landscape of Oncogene Targeted Therapies (ESMO and WCLC Recap)

*October 2022*

There was a focus on treating EGFR-positive NSCLC that has progressed after being treated with currently approved EGFR targeted therapies, with several presentations of new drug combinations and new EGFR targeted therapies.

  • Data from the CHRYSALIS-2 trial was presented looking at giving a combination of the new EGFR inhibitor called Lazertinib, the EGFR and MET targeted therapy Rybrevant (amivantamab)and chemotherapy to treat EGFR-positive NSCLC that had progressed after previous treatment with approved EGFR inhibitors. We saw promising results with an overall response rate of 50% including responses for patients who had their cancer spread to the brain.
  • Very early phase trial data was presented where a combination treatment with the EGFR targeted therapies Tagrisso (osimertinib) and Portrazza (necitumumab) along with the HER2 inhibitor trastuzumab was used to treat EGFR-positive NSCLC that was no longer responding well to standard targeted therapies. There was initial evidence that some patients might respond to treatment and the combination will be reviewed further in a larger trial.
  • Early data was presented on BBT-176, a new EGFR inhibitor that was designed to specifically work when EGFR C797X and/or T790M mutations develop – which can be ways that EGFR-positive NSCLC can become resistant to currently approved EGFR targeted therapies. Newer EGFR inhibitors that were designed to work against mechanisms of resistance are often called “4th generation EGFR inhibitors.” Responses were seen in patients with EGFR-positive lung cancer that had stopped responding to other approved EGFR targeted therapies and had one or both mutations that can be associated with EGFR targeted therapy resistance.