Superior efficacy of immunotherapy‐based combinations over monotherapy for EGFR‐mutant non‐small cell lung cancer acquired resistance to EGFR‐TKIs

Abstract

Background: While prospective clinical studies on immunotherapy in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) are ongoing, this study aimed to investigate the outcomes of immunotherapy combinations in such a population in a real-world setting. Methods: The clinical data of pretreated EGFR-mutated NSCLC patients who acquired EGFR-TKI resistance and received immunotherapy were retrospectively analyzed in this study. Progression-free survival (PFS) was assessed using the Kaplan-Meier log-rank test, and univariate and multivariate analysis were performed. Results: A total of 31 patients were analyzed in this study. A total of 25 (80.6%) patients received combination immunotherapy. In the univariate analysis, patients who received combination immunotherapy seemingly acquired longer PFS than those who received monotherapy, although there was no significant difference (3.42 months vs. 1.61; P = 0.078; hazard ratio (HR) 0.43, 95% CI: 0.16-1.13). Patients who received antiangiogenic drugs prior to immunotherapy acquired better PFS (3.42 months vs. 1.58; P = 0.027; HR 0.37, 95% CI: 0.15-0.93), while patients with liver metastasis had inferior PFS (2.04 months vs. 3.42; P = 0.031; HR 2.83, 95% CI: 1.05-7.60). Furthermore, multivariate analysis confirmed that the above three factors had independent prognostic value. Conclusions: The study revealed that immunotherapy combinations are better choices than single-agent regimens in previously treated and EGFR-mutant NSCLC patients with progressive disease. In addition, antiangiogenic drugs administered before immunotherapy might be a favorable prognostic factor, while liver metastasis was associated with a short PFS in this setting. In future, more robust and prospective clinical trial results are expected to guide clinical practice.

Different prognostic implications of hepatic metastasis according to front-line treatment in non-small cell lung cancer: a real-world retrospective study

“…However, unlike cytotoxic chemotherapy and targeted therapy, there is still debate about the effect of liver metastasis on the prognosis of patients who receive immunotherapy. Some studies have identified liver metastasis as an independent poor prognostic factor in patients who received immunotherapy (17,18); conversely, the presence of liver metastasis did not affect prognosis in other studies (19,20).…”

Immune checkpoint inhibitors for RET fusion non-small cell lung cancer: hopes and challenges

“…In a study of EGFR mutant lung adenocarcinoma found that after the treatment of Erlotinib, the absence of ‘killer T cells’ and ‘highly infiltrated helper T cells’ improved significantly in the tumor microenvironment. Other studies also revealed that inhibit the driver gene and its downstream pathways will up-regulate major histocompatibility complex -1 and then it can recognize antigens, thus promote the activity of CD8 TILs [37]. It indicated that ICIs may also have great potential in postline treatment with RET fusion NSCLC.…”

MMP11 is associated with the immune response and immune microenvironment in EGFR-mutant lung adenocarcinoma

“…The primary therapy for LUAD with EGFR gene mutations is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) ( 3 ). However, a new obstacle has emerged in treating these patients: EGFR-TKI resistance can occur either primary or secondary, regardless of the generations ( 4 , 5 ). Currently, immune checkpoint inhibitors (ICIs) have significantly improved the treatment of LUAD ( 6 ).…”