Implication of PD­L1 polymorphisms rs2297136 on clinical outcomes of patients with advanced NSCLC who received PD­1 blockades: A retrospective exploratory study.

Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades.

Clinical outcomes and safety of osimertinib plus anlotinib for patients with previously treated EGFR T790M-positive NSCLC: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Although osimertinib achieved convincing efficacy for patients with EGFR T790M-positive non-small-cell lung cancer (NSCLC) as second-line treatment in the AURA3 clinical trials, patients developed drug resistance ultimately. Therefore, the present study was to investigate the clinical outcome and safety of osimertinib plus anlotinib for patients with previously treated EGFR T790M-positive NSCLC. METHODS: Designed as a retrospective study, this study consecutively included a total of 33 patients with advanced NSCLC who possessed a EGFR T790M-positive mutation and progressed after the first-line therapy. Eligible patients were treated with osimertinib plus anlotinib. Baseline characteristics of the patients were collected during hospitalization. Efficacy of the combination regimen was assessed with the change of target lesion using imaging evidence according to RECIST 1.1 criteria, and all the patients were followed up regularly. Adverse reactions were collected and documented during the treatment. Univariate analysis according to baseline characteristic subgroups was performed using log-rank test, and multivariate analysis was carried out by Cox regression analysis. RESULTS AND DISCUSSION: The best overall response of the patients during osimertinib and anlotinib combination indicated that complete response was found in one patient, partial response was observed in 26 patients, stable disease was noted in 5 patients and progressive disease was reported in one patient. Therefore, objective response rate (ORR) of the combination regimen was 81.8% (95%CI: 64.5%-93.0%), and disease control rate (DCR) was 97.0% (95%CI: 84.2%-99.9%). Furthermore, the median progression-free survival (PFS) of the 33 patients with NSCLC was 15.5 months (95%CI: 6.19-24.81). In addition, the median overall survival (OS) of the 33 patients with NSCLC was 23.8 months (95% CI: 17.67-29.93). Safety profile suggested that the most common adverse reactions of the patients with NSCLC who received anlotinib plus osimertinib were hypertension (63.6%), fatigue (57.6%), diarrhoea (48.5%%), dermal toxicity (39.4%) and proteinuria (33.3%). Interestingly, multivariate Cox regression analysis for PFS demonstrated that ECOG performance status was an independent factor to predict the PFS of the combination regimen. WHAT IS NEW AND CONCLUSION: Osimertinib plus anlotinib regimen preliminarily exhibited encouraging clinical outcomes and acceptable safety profile for patients with previously treated EGFR T790M-positive NSCLC numerically. This conclusion should be validated in prospective clinical trials.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study.

PURPOSE: The present study was to investigate the real-world efficacy and safety of anlotinib monotherapy as third-line therapy for elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 83 elderly patients (>65 years) with NSCLC who were progressed at least two lines of previous systemic therapy were recruited retrospectively. Patients were treated with anlotinib monotherapy (12 mg or 10 mg). Efficacy of anlotinib was assessed and all the patients were followed up regularly. Adverse reactions were collected during anlotinib administration. Univariate analysis was performed using Log rank test and multivariate analysis was adjusted by Cox regression analysis. Additionally, prognostic analysis according to common adverse reactions was implemented to identify the potential clinical significance. RESULTS: The best overall response of the 83 elderly patients during anlotinib monotherapy indicated that partial response (PR) was observed in six patients, stable disease (SD) was noted in 59 patients, and progressive disease (PD) was reported in 18 patients. Consequently, the objective response rate (ORR) was 7.2% (95% CI=2.7-15.1%) and the disease control rate (DCR) was 78.3% (95% CI=67.9-86.6%). The median progression-free survival (PFS) of the 83 elderly patients with NSCLC was 4.2 months (95% CI=3.51-4.89). Furthermore, the median overall survival (OS) of the 83 patients was 9.6 months (95% CI=6.65-12.55). The safety profile suggested that the relatively common adverse reactions of the elderly patients with ES-SCLC receiving anlotinib therapy were hypertension (49.4%), fatigue (45.8%), and hand-foot syndrome (39.8%). Interestingly, association analysis exhibited that the median PFS of patients with hypertension and non-hypertension was 4.5 and 3.0 months, respectively (χ 2=6.306, P=0.012). CONCLUSION: Anlotinib monotherapy demonstrated a satisfactory efficacy and tolerable safety profile in third-line settings for elderly patients with advanced NSCLC. Patients who experienced a hypertension adverse reaction induced by anlotinib therapy might confer superior PFS. The conclusion should be validated in prospective clinical trials subsequently.