Canadian Consensus: A New Systemic Treatment Algorithm for Advanced EGFR-Mutated Non-Small-Cell Lung Cancer

Background: Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised: (1) What is the optimal first-line treatment for patients with EGFR-mutated nsclc? (2) What is preferred first-line treatment for patients with brain metastasis? (3) What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)? (4) What is the preferred treatment after osimertinib? (5) What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods: A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results: The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions: This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.