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)

Abstract

Introduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the rst-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 rst-line Alectinib as ALK-TKI.Materials and Methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a rst-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 signi cantly higher in the high-positive group (87.2 vs. 68.5%; p=0.002). According to the cutoff 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 e cacy of alectinib varies signi cantly across patient subgroups with different percentages of ALK-positive cells. If these ndings are prospectively validated, the percentage of ALK-positive cells may be used as a strati cation factor in randomized trials comparing different ALK-TKIs.

Issues with the targeted therapy of non‑small cell lung cancer with thyroid metastases: A case report

“…The present study aimed to draw attention to the fact that the difference in ALK percentages between patients may also differ in metastatic tissues of the same patient. In the case described herein, a low ALK percentage positivity in the lung tissue may explain the weak response in the lung ( 19 ).…”

Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?

“…For example, in the TOGA study, in which the addition of trastuzumab to systemic chemotherapy in metastatic gastric cancer was investigated the most benefit was observed in the group with immunohistochemically (IHC) HER2-positive 3+/ in-situ hybridization (ISH)+ with proportionately less benefit in the IHC 2+/ISH+ and IHC1+/ISH+ subgroups ( 23 ). Similarly, it has been reported that the percentage of ALK-positivity in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is correlated with response and survival ( 24 ).…”

Low level ALK FISH positive results should be approached with caution and confirmed by an orthogonal method

“…Typically, discrepancies, such as false-positive FISH results, are observed with low levels (15–25%) of ALK FISH positivity ( 10 - 13 ). Interestingly, a couple of studies have shown an association between low FISH positivity and a low response rate to ALK inhibitors ( 14 - 16 ).…”