The Efficacy and Safety of Anlotinib Alone and in Combination with Other Drugs in Advanced Lung Cancer: A Retrospective Cohort Study.

OBJECTIVE: Lung cancer is a disease associated with high levels of morbidity and mortality, with approximately 2.1 million new cases every year. Anlotinib is a new small-molecule multitarget tyrosine kinase inhibitor independently developed in China that can inhibit the formation of tumor blood vessels and has a therapeutic effect on various cancers. However, the application of anlotinib in lung cancer needs further investigation. METHODS: We collected the progress notes of 43 patients with advanced lung cancer treated at the Oncology Department of Guangzhou Chest Hospital from March 2019 to March 2021. Additionally, we assessed the differences between drug combination therapy and single-drug therapy among patients treated with anlotinib. RESULTS: Patients in both the anlotinib-combination and anlotinib-monotherapy groups experienced remission; however, the overall disease control rate in the anlotinib-combination group was higher than that in the anlotinib-monotherapy group. Reexamination via computed tomography showed that patients in the anlotinib-combination group had better recovery than those in the anlotinib-monotherapy group. Although the overall incidence of adverse reactions in the anlotinib-combination group was higher than that in the monotherapy group, most of the adverse reactions were I-II levels and improved after symptomatic treatment. CONCLUSION: Anlotinib combined with other therapies is better than anlotinib alone for the management of patients with advanced lung cancer.

Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in non-small cell lung cancer (NSCLC) but there is a lack of clinical data on the correlation of MET amplification with the ICI response in NSCLC. METHODS: Copy number alteration (CNA), somatic mutation, and clinical data from two immunotherapy cohorts (Rizvi et al. cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC [lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)] data-set. RESULTS: In the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039; HR =0.37; 95% CI: 0.18-0.73). In the TCGA-NSCLC data-set, MET amplification was associated with high MET mRNA and protein levels, tumor mutation burden (TMB), neoantigen load (NAL), immune-activated cell patterns, immune-related gene expression levels, and the number of gene alterations in the DNA damage response and repair (DDR) pathway. Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group. CONCLUSIONS: Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.

Concomitant Pulmonary Tuberculosis Impair Survival in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinoma Patients Receiving EGFR-Tyrosine Kinase Inhibitor.

OBJECTIVE: Limited studies have clearly demonstrated the effect of EGFR-TKI in the treatment of EGFR mutant NSCLC patients with underlying pulmonary disease, like pulmonary tuberculosis (PTB). Here, we conducted the study to evaluate the impact of PTB on survival of Chinese EGFR mutant lung adenocarcinoma (LUAD) patients that underwent EGFR-TKI treatment. METHODS: Clinicopathologic data of 1448 LUAD patients harboring EGFR mutations from the Guangzhou Chest Hospital between 2017 and 2019 were reviewed retrospectively. Patients receiving EGFR-TKI treatment were divided into PTB and non-PTB groups. The differences in response to EGFR-TKIs and survival between the two groups were assessed. RESULTS: After EGFR-TKIs treatment, the objective response rate (58.14% vs 47.62%) as well as disease control rate (97.67% vs 85.71%) were higher in the non-PTB group than in the PTB group, but there was no statistical difference. In the survival analysis, both the median progression-free survival (7.47 months vs 11.77 months, p = 0.038) and the overall survival (13.00 months vs 20.00 months, p = 0.001) were significantly shorter in the PTB group than in the non-PTB group. Furthermore, for patients with 19Del mutation, or metastases sites less than 3, or using first-line EGFR-TKI, EGFR-TKIs treatment significantly prolonged the median PFS and OS in patients without PTB. CONCLUSION: LUAD patients with concomitant PTB have a poor response to EGFR-TKI treatment, especially in terms of survival outcome.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing.

PURPOSE: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. MATERIALS AND METHODS: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. RESULTS: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. CONCLUSION: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.

Hyaluronic acid-modified selenium nanoparticles for enhancing the therapeutic efficacy of paclitaxel in lung cancer therapy.

Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. In this paper, selenium nanoparticles (SeNPs) was linked with hyaluronic acid (HA) to prepare tumor-targeted delivery vehicle HA-SeNPs, and HA-SeNPs was loaded with paclitaxel (PTX) to fabricate functionalized selenium nanoparticles HA-Se@PTX. HA-Se@PTX showed greater uptake in A549 cells in comparison with that in HUVEC, verifying HA-mediated specific uptake of HA-Se@PTX. HA-Se@PTX was capable of entering A549 cells via clathrin-associated endocytosis and showed faster drug release in cancer cell microenvironment in comparison with normal physiological environment. HA-Se@PTX could obviously inhibit the proliferation, migration and invasion of A549 cells and trigger A549 cells apoptosis. Moreover, active targeting functionalized selenium nanoparticles HA-Se@PTX showed greater in vivo antitumor activity compared with free PTX or passive targeting delivery system Se@PTX. In addition, HA-Se@PTX exhibited negligible toxicity on the major organs of mice. In a word, HA-Se@PTX may develop into a valuable nanoscale antitumor drug agent for lung cancer treatment.