Prevalence and Clinical Impact of Concomitant Mutations in Anaplastic Lymphoma Kinase Rearrangement Advanced Non-small-Cell Lung Cancer (Guangdong Association of Thoracic Oncology Study 1055)

Abstract

Background: In patients with anaplastic lymphoma kinase (ALK) rearrangement-positive advanced non-small-cell lung cancer (NSCLC), ALK inhibitors are now the standard treatment, but their clinical efficacy varies widely for each patient. In this multicenter retrospective study, we evaluated the clinical efficacy of crizotinib according to the ALK rearrangement variants and concomitant mutations present. Patients and Methods: A total 132 patients with ALK rearrangement advanced NSCLC from 4 centers in Guangdong province, China were evaluated. All patients received crizotinib treatment and their ALK rearrangement status was identified by next-generation sequencing (NGS). Results: The median progression-free survival (PFS) in patients with EML4-ALK rearrangement (n = 121), non-EML4-ALK rearrangement (n = 5), and EML4-ALK arrangement accompanied by non-EML4-ALK rearrangement (n = 6) was 12.8, 7.5, and 7.4 months, respectively, with no significant difference between them (p = 0.1554). Similarly, among patients with various EML4-ALK variants (variant 1, variant 3a/b, and other variants), the median PFS values were again comparable. According to baseline NGS data, the median PFS in patients who had ALK rearrangement only, ALK rearrangement and concomitant tumor-suppressor gene mutations, and ALK rearrangement and concomitant oncogene mutations was 14.2, 10.9, and 4.9 months, respectively; (p = 0.0002). A multivariable analysis indicated that concomitant oncogene mutations and tumor-suppressor gene mutations were both negative factors influencing the efficacy of crizotinib in ALK rearrangement NSCLC. Li et al. Concomitant Mutations in ALK Rearrangement NSCLC Conclusion: Concomitant oncogene mutations and tumor-suppressor gene mutations had negative effects on the efficacy of crizotinib, while various ALK variants had a similar influence.

Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib

“…Besides, in our study, NGS identified TP53 mutations to be the most common type of concomitant mutation with ALK rearrangement, with an incidence of 24%, which was comparable to the 20-29% reported by other investigators (1,41). In addition to identifying the mutations concomitant with ALK rearrangement, we also analyzed the relationships of these combinations with prognosis.…”

“…Lung cancer remains the most common malignancy worldwide, the morbidity and mortality of which are at the forefront of global research (1). With the recent development in targeted therapy, treatment for patients with non-small cell lung cancer (NSCLC) has changed substantially (2).…”

Alk-rearranged lung adenocarcinoma: From molecular genetics to therapeutic targeting

“…Li and coworkers reported in 132 NSCLC patients with ALK rearrangement a frequency of 0.76% of KRAS mutations and 2.3% of EGFR mutations. 19 The fundamental role of EML4-ALK fusion gene in the pathogenesis of ALK-rearranged LUADs was directly supported through the study of transgenic mouse lines that express EML4-ALK specifically in lung alveolar epithelial cells: all these transgenic mice developed adenocarcinoma nodules in lungs a few weeks after birth. 20 These tumors were exquisitely sensitive to ALK-TKIs.…”

Effect of ultrasound-guided pulsed radiofrequency on intercostal neuralgia after lung cancer surgery

“…Lung cancer is one of the most frequently diagnosed cancers around the world. [1][2][3][4] It is also the leading cause of highest mortality and morbidity in such patients. [5][6][7][8] Surgery is recommended for lung cancer as one of the most effective management.…”

“…Lung cancer is one of the most frequently diagnosed cancers around the world [1–4] . It is also the leading cause of highest mortality and morbidity in such patients [5–8] .…”