New Designations and Efficacy Demonstrations Push the EGFR+ NSCLC Paradigm Forward

The utility of EGFR TKIs in select subgroups of patients with EGFR-mutant metastatic non–small cell lung cancer (NSCLC), as well as their role in the adjuvant setting, are beginning to be teased out, explained Timothy F. Burns, MD, PhD.

“We have very good EGFR inhibitors,” said Burns. “When patients progress, most of the [resistance] mechanisms are not through EGFR, so we’re clearly hitting the target hard enough However, the medications do not work forever. We are not curing our patients in the metastatic setting with an EGFR-directed TKI.”

With regard to earlier-generation EGFR TKIs, findings from the phase 3 RELAY trial led to the May 2020 approval of ramucirumab (Cyramza) and erlotinib (Tarceva) for the frontline treatment of patients with EGFR-mutant metastatic NSCLC. The combination induced a 41% reduction in the risk of disease progression or death compared with erlotinib alone (HR, 0.59; 95% CI, 0.46-0.76; P < .0001).

With the approval of ramucirumab/erlotinib, certain questions have been brought to light. Specifically, whether patients from Asia and those with L858R mutations, who did not derive a significant benefit from osimertinib, should be treated with the combination regimen.

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