Debate on first-line treatment strategies in advanced non-small cell lung cancer with EGFR mutation: An expert panel meeting by the Italian Association of Thoracic Oncology (AIOT).

Background: The front-line treatment options and regulatory approval scenario for epidermal growth factor receptor (EGFR) mutation positive metastatic non-small cell lung cancer (NSCLC) have rapidly evolved in the recent months, with newly presented positive trial results of novel compounds and combination strategies in the setting of common activating mutations, uncommon mutations, and exon 20 insertions. In this context, international lively debate is emerging on how to choose among the available regimens, based on efficacy and safety results.

Methods: A virtual International Expert Panel was held in July 2024 to review data on front-line regimens in patients with NSCLC harboring EGFR mutations, including common, uncommon and exon 20 insertions. The panel discussed available evidence, and reached common considerations for clinical practice and clinical research.

Results: In the setting of EGFR common activating mutations, all panelists agreed that single agent osimertinib, the combination of osimertinib with platinum-pemetrexed, and the combination of amivantamab and lazertinib, are first-line treatment options. Overall, panelists defined characteristics of patients in which combination treatments should be avoided. Subsequent treatment strategies at disease progression were discussed according to the different front-line options. With regards to uncommon EGFR mutations, panelists agreed that afatinib remains the only drug with phase 3 results available, and that afatinib and osimertinib are the preferred first-line options. In EGFR exon20 insertion positive disease, the combination of carboplatin, pemetrexed and amivantamab has been identified as the preferred front-line treatment, with second-line amivantamab to be used in the second-line setting whenever not available in front-line. The panelists defined priorities in clinical research, with high priority attributed to investigating resistance mechanisms, novel generation of tyrosine kinase inhibitors, and selection biomarkers.

Conclusions: Different toxicity profiles and sequential strategies were considered, together with efficacy results, to reach common considerations for the front-line treatment strategies in EGFR mutant NSCLC, however clinical research should be prioritized to identify further selection features.