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

Radiotherapy with continued EGFR‐TKIs for oligoprogressive disease in EGFR‐mutated non‐small cell lung cancer: A real‐world study

“… 4 , 5 The therapeutic strategy beyond progression needs to be determined according to the progression patterns. 11 For the oligoprogressive disease, discontinuation of TKIs may result in the regrowth of TKIs‐sensitive clones and rapid tumor regrowth. In addition, the oligoprogressive disease might be treated with radiotherapy, whereas EGFR‐TKIs can be preserved and continued.…”

“…In our study, patients treated with EGFR‐TKIs had a median PFS1 of 11.0 months, consistent with previous studies. 9 Although it has been demonstrated that radiotherapy obtained good local control rates in NSCLC patients with oligometastatic disease at diagnosis, 9 , 11 , 12 , 13 data on the efficacy of local therapy such as radiotherapy on oligoprogressive disease after target therapy is scarce. 9 , 14 A recent study showed that local ablative therapy (radiation or surgery) and continuation of TKIs could extend disease control by >6 months in patients with ALK + or EGFR ‐MT NSCLC on erlotinib or crizotinib therapy who developed oligoprogressive disease.…”

The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

“…Notably, the solid tumor microenvironment exhibits characteristics that attenuate efficient antitumor immune response [180,181]. Metabolic deregulations are associated with carcinogenesis, e.g., increased serum insulin levels and free IGF-1 favor cell proliferation and affect the immune response pushing the cellular microenvironment towards carcinogenesis [182][183][184][185].…”

Fibroblast Growth Factor Inhibitors for Treating Locally Advanced/Metastatic Bladder Urothelial Carcinomas via Dual Targeting of Tumor-Specific Oncogenic Signaling and the Tumor Immune Microenvironment

“…Lenvatinib, a multiple TKI that inhibits VEGFR1-3, FGFR1-4, PDGFRα, c-KIT, and RET [72], is a potent angiogenesis inhibitor and also an effective immunomodulator [72,73]. The dual inhibitory activity of lenvatinib against both VEGF and FGF induced broadspectrum antitumor activity due to its antiangiogenic effects [73].…”