Tumors undergo fast neovascularization to support the rapid proliferation of cancer cells. Vasculature in tumors, unlike that in wound healing, is immature and affects the tumor microenvironment, resulting in hypoxia, acidosis, glucose starvation, immune cell infiltration, and decreased activity, all of which promote cancer progression, metastasis, and drug resistance. This innate defect of tumor vasculature can however represent a useful therapeutic target. Angiogenesis inhibitors targeting tumor vascular endothelial cells important for angiogenesis have attracted attention as cancer therapy agents that utilize features of the tumor microenvironment. While angiogenesis inhibitors have the advantage of targeting neovascularization factors common to all cancer types, some limitations to their deployment have emerged. Further understanding of the mechanism of tumor angiogenesis may contribute to the development of new antiangiogenic therapeutic approaches to control tumor invasion and metastasis. This review discusses the mechanism of tumor angiogenesis as well as angiogenesis inhibition therapy with antiangiogenic agents.

Secondary sarcopenia is defined as a decrease in muscle mass due to disease or malnutrition. Several studies have reported that secondary sarcopenia is an indicator of postoperative recurrence. We hypothesized that there is a correlation between the effect of immune checkpoint inhibitors (ICIs) and sarcopenia. We retrospectively analyzed 38 patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICIs between February 2016 and April 2018. Patients were divided into two groups according to the change rate of the psoas major muscle area (PMMA) at the L2–L3 position and investigated the correlation between the change rate of the PMMA and the efficacy of ICIs was investigated. The objective response and disease control rates were lower in patients with sarcopenia than in those without sarcopenia. Patients with sarcopenia exhibited a significantly shorter median progression-free survival (PFS) than non-sarcopenia patients. Moreover, focusing on good Eastern Cooperative Oncology Group performance status patients, sarcopenia patients showed a shorter PFS than non-sarcopenia patients. Patients with sarcopenia are associated with poor outcomes for immunotherapy among those with advanced NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders.

Little is known regarding the effectiveness and tolerability of immune checkpoint inhibitor (ICI) rechallenge after disease progression following initial ICI treatments. To identify eligible patients for ICI rechallenge, we retrospectively analyzed the relationship between clinical profiles and the effect of ICI rechallenge in patients with non-small cell lung cancer (NSCLC). We enrolled 35 NSCLC patients at six different institutions who were retreated with ICIs after discontinued initial ICI treatments due to disease progression. Cox proportional hazards models were used to assess the impact of clinical profiles on overall survival (OS) and progression-free survival (PFS). Median PFS and OS were 81 d (95% confidence interval, CI, 41–112 d) and 225 d (95% CI 106–361 d), respectively. The objective response rate was 2.9%, and the disease control rate was 42.9%. Multivariate analysis demonstrated that Eastern Cooperative Oncology Group Performance Score (ECOG-PS) ≥ 2 (hazard ratio, HR, 2.38; 95% CI 1.03–5.52; p = 0.043) and body mass index (BMI) > 20 (HR 0.43, 95% CI 0.19–0.95, p = 0.036) were significantly associated with PFS of ICI rechallenge. Our observations suggest that poor ECOG-PS and low BMI at intervention with ICI rechallenge may be negative predictors for ICI rechallenge treatment in patients with NSCLC.

Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies. Thus, we aimed to examine whether these factors could also be prognostic markers for chemoimmunotherapy. We retrospectively examined 237 patients with advanced NSCLC treated with chemoimmunotherapy. In the total group, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 8.6 months. Multivariate analysis of OS and PFS revealed significant differences based on PNI and LIPI. Programmed cell death ligand 1 (PD-L1) was also significantly associated with OS and PFS. PNI and a PD-L1 tumor proportion score (TPS) of <50% and poor LIPI (regardless of PD-L1 TPS) were associated with poor prognosis. PNI and LIPI predicted survival outcomes in patients with advanced NSCLC treated with chemoimmunotherapy, especially in patients with PD-L1 TPS <50%. For patients in this poor category, chemoimmunotherapy may result in a worse prognosis than expected.

Background: Durvalumab consolidation after chemoradiotherapy (CRT) is a standard treatment for locally advanced non-small cell lung cancer (NSCLC). However, studies on immunological and nutritional markers to predict progression-free survival (PFS) and overall survival (OS) are inadequate. Systemic inflammation causes cancer cachexia and negatively affects immunotherapy efficacy, which also reflects survival outcomes. Patients and Methods: We retrospectively investigated 126 patients from seven institutes in Japan. Results: The modified Glasgow Prognostic Score (mGPS) values, before and after CRT, were the essential predictors among the evaluated indices. A systemic inflammation-based prognostic risk classification was created by combining mGPS values before CRT, and C-reactive protein (CRP) levels after CRT, to distinguish tumor-derived inflammation from CRT-induced inflammation. Patients were classified into high-risk (n = 31) and low-risk (n = 95) groups, and the high-risk group had a significantly shorter median PFS of 7.2 months and an OS of 19.6 months compared with the low-risk group. The hazard ratios for PFS and OS were 2.47 (95% confidence interval [CI]: 1.46–4.19, p < 0.001) and 3.62 (95% CI: 1.79–7.33, p < 0.001), respectively. This association was also observed in the subgroup with programmed cell death ligand 1 expression of ≥50%, but not in the <50% subgroup. Furthermore, durvalumab discontinuation was observed more frequently in the high-risk group than in the low-risk group. Conclusion: Combining pre-CRT mGPS values with post-CRT CRP levels in patients with locally advanced NSCLC helps to predict the PFS and OS of durvalumab consolidation after CRT.

Editorial Commentary Lorlatinib in ALK-positive non-small cell lung cancer: final survival data that reshape the therapeutic landscape Yuki Katayama