Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50%

IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P < 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group.ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%

Advanced Non-Small-Cell Lung Cancer in Elderly Patients: Patient Features and Therapeutic Management

Lung cancer has the highest mortality rate among all cancers in most developed countries. The number of elderly patients with lung cancer has been increasing, reflecting the global increase in aging population. Therefore, standard chemotherapeutic regimens for elderly patients with lung cancer need to be established. However, the effectiveness of chemotherapy in elderly patients with advanced non-small-cell lung cancer remains controversial because they are often excluded from clinical trials. Some clinical trials have shown that the therapeutic benefit of a third-generation anticancer drug alone was superior to best supportive care. In contrast, platinum-doublet was superior only in terms of overall survival and progression-free survival, and other trials reported an increased rate of treatment-related death in the elderly patients. In recent years, some novel treatment modalities for lung cancer have been developed and shown to significantly improve the therapeutic outcomes, including targeted therapy for lung cancer harboring driver mutation, combination therapy of angiogenesis inhibitor and cytotoxic agents, and immune checkpoint inhibitor. Although several clinical trials with these agents have shown favorable outcome regardless of age, their safety in the elderly patients has not been established. Herein, we discuss the current clinical status and future prospects in elderly patients with lung cancer

Tumor Neovascularization and Developments in Therapeutics

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

Safety and Usefulness of Cryobiopsy and Stamp Cytology for the Diagnosis of Peripheral Pulmonary Lesions

Reports on the use of cryobiopsy (CB) for lung cancer diagnosis are limited. The aims of the present study were to evaluate the safety and usefulness of CB using radial endobronchial ultrasonography, without a guide sheath, for the diagnosis of peripheral pulmonary lesions and determine the utility of stamp cytology, an on-site diagnostic technique for determining tumor inclusion in CB samples. We retrospectively analyzed data for 35 patients (36 lesions) with suspected peripheral lung cancer who underwent CB between August 2017 and February 2019 at our medical facility. The diagnostic yield, incidence of complications, and the utility of stamp cytology for diagnosis were investigated. The diagnostic yield of CB was 86.1% (31/36) with histological diagnosis, and 80.5% (29/36) with diagnosis using stamp cytology; the overall yield was 91.6% (33/36). Pneumothorax requiring thoracic drainage occurred in two patients, both of whom had lesions contacting the pleura. Grade 2 and grade 1 bleeding occurred in one and 25 patients, respectively. CB enables the collection of very large, nearly intact tissue samples, thus resulting in an improvement in the true diagnosis rate and facilitating the measurement of multiple biomarkers as well as rapid histological diagnosis

Nicotine Induces Resistance to Erlotinib Therapy in Non-Small-Cell Lung Cancer Cells Treated with Serum from Human Patients

Previously, we reported that nicotine reduces erlotinib sensitivity in a xenograft model of PC9, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-sensitive non-small-cell lung cancer cell line. The present study examined whether smoking induces erlotinib resistance in vitro. We assessed resistance to EGFR-TKIs by treating cancer cell lines with erlotinib, afatinib, or osimertinib, and serum collected from smokers within 30 min of smoking and that from a non-smoker as a control. We also assessed erlotinib resistance by treating PC9 cells exposed to serum from a smoker or a non-smoker, or serum from an erlotinib user. Treatment of the cancer cell lines with serum from smokers induced significant erlotinib resistance, compared with the control (p < 0.05). Furthermore, serum samples with a high concentration of cotinine (a nicotine exposure indicator) demonstrated stronger erlotinib resistance than those with low concentrations. Similar to the observations with erlotinib treatment of cell lines, the analysis of serum from erlotinib users revealed that smokers demonstrated significantly reduced sensitivity to erlotinib (p < 0.001). In conclusion, our present results support the hypothesis that smoking contributes to resistance to erlotinib therapy in non-small-cell lung cancer

Impact of bowel movement condition on immune checkpoint inhibitor efficacy in patients with advanced non‐small cell lung cancer

Background Cancer immunotherapy is under development as a promising alternative strategy for treating advanced non‐small cell lung cancer (NSCLC). However, the development of novel biomarkers to optimize the use of immune checkpoint inhibitors (ICIs) is still ongoing. Gut microbiota are known to regulate a host's immunity and are associated with the response to ICIs in melanoma. Therefore, we analyzed the association between ICI treatment efficacy and bowel movement condition in patients with NSCLC. Methods This retrospective study analyzed patients with advanced NSCLC who were treated with ICIs between December 2015 and March 2018 at University Hospital Kyoto Prefectural University of Medicine in Kyoto, Japan. The association between stool abnormalities and ICI efficacy was investigated. We defined patients with constipation or those who used a laxative as the stool abnormality group. Results We retrospectively enrolled 40 patients with advanced NSCLC who were treated with ICIs. The median age was 69.5 years; 20 patients had a stool abnormality and 20 patients did not. The disease control rates were lower in NSCLC patients with stool abnormalities than in those without stool abnormalities (20% vs. 77.8%, respectively; P = 0.0016). The time to treatment failure with ICI treatment was shorter in NSCLC patients with stool abnormalities compared with those without stool abnormalities (P = 0.003; odds ratio, 3.09; 95% confidence interval 1.41–6.78). Conclusion Stool abnormality might be a predictive biomarker for the clinical benefit of ICI treatment in patients with NSCLC. Further investigations are warranted to validate our findings