The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study).

INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.

Prognostic value of expression levels of miR-148a, miR-152 and HLA-G in colon cancer.

Aberrant expression of human leukocyte antigen G (HLA-G), an immunosuppressive molecule, has been observed in various cancer types. The exact mechanism of HLA-G expression is unclear. HLA-G expression is associated with low expression levels of microRNA (miR)-148a and miR-152. To the best of our knowledge, the prognostic value of the expression levels of miR-148a, miR-152 and HLA-G has not been investigated in colon cancer. The aim of the present study was to investigate the relationship between the presence of HLA-G molecules and the expression levels of miR-148 and miR-152 in colon cancer. In addition, the association of both HLA-G and miR expression with survival results and clinicopathological data was determined. An immunohistochemical method was used for detection of HLA-G expression in the tumor tissues and adjacent healthy tissues of 108 patients with colon cancer. Reverse transcription-quantitative PCR was used for miR analysis. HLA-G was expressed in 82 (75.9%) of the cancer samples, and there was no staining in normal tissues. HLA-G expression >20%, which was found in 41.7% (45/108) of the patients with colon cancer, was significantly positively associated with patient survival (P=0.039). Additionally, miR-148a levels were lower in the tumor tissues compared with the adjacent healthy tissues. No differences were found for miR-152 expression. In addition, mir-148a levels were found to be significantly lower (P=0.001) in HLA-G-positive tumor tissues than HLA-G-negative tumor tissues, but no such relationship was found for miR-152 levels. The presence of HLA-G expression was associated with poor survival outcomes. HLA-G is one of the prognostic factors in colon cancer, and decreased miR-148a expression in colon cancer tissues may be associated with HLA-G-mediated carcinogenesis.