Current challenges of unresectable stage III NSCLC: are we ready to break the glass ceiling of the PACIFIC trial?

Abstract

Consolidation anti-programmed death-ligand 1 has become a new standard of care in unresectable stage III non-small cell lung cancer (NSCLC) following chemo-radiotherapy (CTRT), based on the results of two phase III trials. Advances remain however needed, in particular to reduce the risk of distant relapse and for treatment personalization. Newer strategies are currently being tested, including consolidation with dual immune checkpoint inhibitors (ICIs), concurrent chemo-radioimmunotherapy and (chemo)-immunotherapy induction before CTRT. One randomized phase II reported better outcomes with a double ICI consolidation as compared with durvalumab alone. Three nonrandomized phase II trials also suggested that concurrent ICI-CTRT was feasible. Within this review, we summarize the current evidence, highlight ongoing trials and discuss challenges that will ideally lead to a cure for more patients with unresectable stage III NSCLC.

Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients

“…Immunosenescence describe the process through which the immune system is assumed to become less capable of performing its functions properly ( 11 , 12 ). There is growing evidence that the immune response of the elderly to cancer may be diminished or compromised for the following reasons: (1) they have fewer naïve B and T cells, which could leave gaps in their repertoire for neoantigens; (2) their memory T cells, which are capable of recognizing tumor cells, have become exhausted; (3) their immune systems have more immune-suppressive cells ( 13 , 14 ), and (4) alteration of response of macrophages, and neutrophils with age that are necessary for T cell activation in order to eliminate cancer ( 15 ) ( Figure 1 ).…”

Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy

“…Stage III non-small cell lung cancer (NSCLC) is a locally advanced malignancy with adverse prognostic factors in the primary tumor and/or regional lymph node metastasis [ 1 ]. A considerable proportion of these patients have N2 disease, indicating mediastinal lymph node involvement, and are potentially resectable [ 2 ].…”