Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer: End of the Road or the First Chapter?
Mené sur 492 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde avec mutation au niveau du gène EGFR et de stade métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout de pembrolizumab à une chimiothérapie (pémétrexed et sels de platine), après l'échec d'un traitement par inhibiteur de tyrosine kinase du récepteur EGFR
In patients with common EGFR-mutant metastatic non–small cell lung cancer (NSCLC), although frontline EGFR tyrosine kinase inhibitor (TKI) monotherapy, especially osimertinib, has been standard, treating patients with acquired resistance remains challenging. On-target resistance mechanisms are uncommon and fourth-generation EGFR kinase inhibitors remain in development. Targeting bypass track signaling has been problematic because of the infrequent occurrence of novel drivers and no clear regulatory path for approval/reimbursement.1 Although targeting MET signaling with selective MET inhibitors has shown early promise, optimal MET assessment methods remain debated and registrational trial results are awaited. Alongside these issues, histologic transformation often portends poor outcomes, especially for those with the baseline EGFR-TP53-RB1 mutation triplet. Hence, for the vast majority, platinum-based chemotherapy is the mainstay treatment, benchmarked by a median progression-free survival (PFS) of 5.4 months.