Beyond First-Line Immunotherapy: Potential Therapeutic Strategies Based on Different Pattern Progressions: Oligo and Systemic Progression

SIMPLE SUMMARY: The aim of this innovative review is to highlight the treatment strategies beyond immune-checkpoint inhibitor (ICI)-based first-line therapy failure according to different patterns of progression (i.e., oligo or systemic progression) and to discuss the ongoing and potential future therapeutic approaches to overcome resistance to immunotherapy. Many therapeutic strategies can be adapted in advanced non-small cell lung cancer patients with oligo and systemic progression to personalize the treatment approach based on to re-characterization of the tumors, previous ICI response and type of progression. ABSTRACT: First-line immune-checkpoint inhibitor (ICI)-based therapy has deeply changed the treatment landscape and prognosis in advanced non-small cell lung cancer (aNSCLC) patients with no targetable alterations. Nonetheless, a percentage of patients progressed on ICI as monotherapy or combinations. Open questions remain on patients’ selection, the identification of biomarkers of primary resistance to immunotherapy and the treatment strategies to overcome secondary resistance to first-line immunotherapy. Local ablative approaches are the main therapeutic strategies in oligoprogressive disease, and their role is emerging in patients treated with immunotherapy. Many therapeutic strategies can be adapted in aNSCLC patients with systemic progression to personalize the treatment approach according to re-characterization of the tumors, previous ICI response, and type of progression. This review’s aim is to highlight and discuss the current and potential therapeutic approaches beyond first-line ICI-based therapy in aNSCLC patients based on the pattern of disease progression (oligoprogression versus systemic progression).