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The objective of this study was to analyze the predictive roles of VEGF/KDR/Ras/MAPK gene expression in patients with advanced non-small-cell lung cancer (NSCLC) treated with bevacizumab plus chemotherapy. Twenty-five patients participating in an open-label phase IV trial (SAİL, MOI9390) with available tumor tissues were analyzed. The mRNA expression levels of VEGF, kinase Insert domain receptor (KDR), Ras, and mitogen-activated protein kinase (MAPK) in tumor tissues were detected using real-time quantitative PCR methods. The relationships between gene expression and disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were assessed. Patients with lower Ras expression had a longer PFS and OS than patients with higher expression (median PFS, 9.9 vs 5.5 months, χ² = 3.944, P= 0.047; OS, 19.3 vs 7.1 months, χ² = 9.384, P = 0.002). The PFS and OS of patients with lower and higher MAPK expression exhibited a marginal and significant difference (median PFS, 9.9 vs 5.5 months, χ² = 3.464, P = 0.063; OS, 19.3 vs 9.7 months, χ² =5.298, P= 0.021), respectively. Multivariate analyses using Cox's proportional hazards model showed that Ras is an independent predictor of OS (χ² = 9.384, P = 0.002). No differences in DCR were found according to Ras expression level. The results indicate that Ras is an independent predictor of OS. Thus, patients with lower Ras expression are most likely to benefit from bevacizumab plus chemotherapy treatment regimen. Patients with higher levels of Ras should receive other inhibitors that target Ras. The results also suggest that gene therapies that decrease RAS expression combined with bevacizumab may improve lung cancer treatment. Although there is a very Important implication to patient selection in the target therapy, the data in this study are very preliminary owing to the too small sample size. Therefore, further research involving large numbers of patients and a prospective assessment of low and high RAS mRNA expressions getting the same treatments need to be done before conclusions can be made. [ABSTRACT FROM AUTHOR]

We evaluated whether tissue tumor mutational burden (tTMB) and STK11 , KEAP1 , and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR / ALK alterations in the phase III KEYNOTE-042 trial. This retrospective exploratory analysis assessed prevalence of tTMB and STK11 , KEAP1 , and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. Of 793 patients, 345 (43.5%) had tTMB ≥175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB ≥175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/exome was not {OS: hazard ratio, 0.62 [95% confidence interval (CI) 0.48-0.80] and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS [hazard ratio (95% CI)] for pembrolizumab versus chemotherapy was observed regardless of STK11 [ STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05)]; KEAP1 [ KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99)], or KRAS [ KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18)] mutation status. tTMB with a cut point of ≥175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score ≥1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11 , KEAP1 , or KRAS mutation status. • Pembrolizumab monotherapy is a standard first-line treatment of patients with PD-L1-positive advanced/metastatic NSCLC. • We assessed clinical utility of potential biomarkers among patients receiving pembrolizumab versus chemotherapy. • tTMB ≥175 mutations/exome was associated with improved outcomes among patients receiving pembrolizumab versus chemotherapy. • tTMB has potential clinical utility as a biomarker for pembrolizumab in first-line PD-L1-positive advanced/metastatic NSCLC. • Pembrolizumab improved overall survival versus chemotherapy regardless of STK11 , KEAP1 , or KRAS mutation status. [ABSTRACT FROM AUTHOR]

Background The OPTIMAL study found that erlotinib improved progression-free survival (PFS) versus standard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). This report describes the quality of life (QoL) and updated PFS analyses from this study. Patients and methods Chinese patients ≥18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received erlotinib (150 mg/day; n = 82) or gemcitabine–carboplatin (n = 72). The primary efficacy end point was PFS; QoL was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, Trial Outcome Index (TOI) and Lung Cancer Subscale (LCS). Results Patients receiving erlotinib experienced clinically relevant improvements in QoL compared with the chemotherapy group in total FACT-L, TOI and LCS (P < 0.0001 for all scales). Erlotinib scored better than chemotherapy for all FACT-L subscales from baseline to cycles 2 and 4 (non-significant). In the updated analysis, PFS was significantly longer for erlotinib than chemotherapy (median PFS 13.7 versus 4.6 months; HR = 0.164, 95% CI = 0.105–0.256; P < 0.0001), which was similar to the previously reported primary analysis. Conclusion Erlotinib improves QoL compared with standard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: In the placebo-controlled phase III SATURN study, maintenance erlotinib after first-line chemotherapy demonstrated significantly prolonged progression-free survival (PFS) and overall survival (OS) in the overall study population of patients with advanced non-small-cell lung cancer (NSCLC). Methods: After four cycles of platinum-based doublet chemotherapy, patients without progressive disease (PD) were randomised to erlotinib (150 mg/day) or placebo until PD or unacceptable toxicity. In this pre-planned analysis, data are assessed according to response to first-line chemotherapy (complete/partial response [CR/PR] or stable disease [SD]). Results: Following first-line chemotherapy, 889 non-PD patients were included in the intention-to-treat population (55% SD; 44% CR/PR; <1% unknown response). Erlotinib maintenance therapy significantly prolonged PFS in both the SD (hazard ratio [HR] = 0.68; P < 0.0001) and CR/PR (HR = 0.74; P = 0.0059) groups, while OS was significantly prolonged in the SD group only (HR = 0.72; P = 0.0019). The erlotinib-related OS benefit in the SD group remained significant across subgroups, irrespective of tumour histology and/or EGFR mutation status. The incidence of adverse events was similar in the SD group and the overall population, and erlotinib treatment did not negatively impact quality of life. Conclusions: Patients with advanced NSCLC and SD following first-line platinum-based doublet chemotherapy derive a significant OS benefit from maintenance erlotinib therapy. [ABSTRACT FROM PUBLISHER]