ensartinib

Anaplastic lymphoma kinase (ALK) fusion gene is one of the most common driver gene in non-small cell lung cancer (NSCLC). Epidemiological data showed that ALK gene fusion is detected in 9.06% of Chinese advanced NSCLC patients. ALK-tyrosine kinase inhibitors (TKIs) have become the standard treatment for advanced NSCLC patients with ALK gene fusion. Seven different ALK-TKIs have been approved by the National Medical Products Administration (NMPA) of China, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib...

BACKGROUND: The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. METHODS: In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal...

Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene detected in approximately 5% of non-small cell lung cancer. However, ALK rearrangement is much less frequent in other solid tumors outside the lungs, such as colorectal cancer (CRC); thus, the optimal management of CRC with ALK rearrangements has yet to be established. In this report, we describe 2 cases of ALK-positive CRC, both of which benefited from ALK tyrosine kinase inhibitor (ALK-TKI) therapy. Case 1 was a postoperative patient with poorly differentiated colon adenocarcinoma, who was diagnosed with metastatic relapse shortly after surgery...

OBJECTIVES: To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). METHODS: The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model...

Anaplastic lymphoma kinase (ALK) fusion represents one of pivotal driver genes within the realm of non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (ALK-TKI) have demonstrated remarkable therapeutic efficacy for patients afflicted with ALK-positive NSCLC. As of June 27, 2023, seven ALK-TKI, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib, have garnered approval from the China National Medical Products Administration (NMPA)(ranking according to the approval time for marketing by NMPA), providing individualized treatment modalities for ALK-positive NSCLC patients...

AIM: This retrospective study aimed to assess the efficacy and safety of ensartinib in Chinese patients with ALK -positive advanced NSCLC in real-world clinical practice. METHODS: Clinical data from ALK -positive NSCLC patients treated with ensartinib in China were collected and analyzed. Efficacy end points included objective response rate and progression-free survival. Safety profiles were also evaluated. RESULTS: A total of 682 patients were included in this study...

Although patients with ALK-positive non-small cell lung cancer (NSCLC) are initially effective on treatment with ALK tyrosine kinase inhibitors (TKIs), resistance will inevitably develop. Of these patients, 2/3 will develop ALK-independent resistance and little is known about the mechanisms of ALK-independent resistance. In pre-clinical studies, the activation of several bypass signaling pathways has been implicated in the development of resistance, including the MET, EGFR, SRC and IGF1R pathways. Among these, the MET pathway is one of the signaling pathways that has recently been extensively studied, and activation of this pathway is one of the mechanisms of ALK-independent drug resistance...

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery...

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive malignant subtype of inflammatory myofibroblastoma (IMT) associated with poor prognosis. IMT can occur in various parts of the body, most frequently in the lungs, followed by the mesentery, omentum, retroperitoneum, and pelvis, among other areas; however, it is exceptionally rare in the stomach. Anaplastic lymphoma kinase (ALK) is a critical driver of lung cancer development and is currently the "gold standard" target for non-small cell lung cancer treatment...

Several cases of STRN-ALK fusion have been reported, and some anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective for treatment. Nevertheless, no cases of COVID-19 leading to heart failure and respiratory failure have been reported in people older than 70 years treated with ALK inhibitors. The present case report describes a 70-year-old patient with usual chronic obstructive pulmonary disease, diabetes, depression, and carotid plaque disease. Next-generation sequencing of tissue obtained by puncture biopsy revealed a STRN-ALK mutation accompanied by a TP53 mutation...

Systemic chemotherapies are the primary treatment options for patients with unresectable and metastatic intrahepatic cholangiocarcinoma (ICC), but the effectiveness of current systemic therapies is limited. The development of targeted-therapy has changed the treatment landscape of ICC, and comprehensive genome sequencing of advanced cholangiocarcinoma patients could be beneficial to identify potential targets to guide individualized treatment. Herein, we reported an unresectable and metastatic ICC patient who detected EML4-ALK rearrangement in peripheral blood, which was later confirmed on tissue-based testing, and achieved partial response (PR) after first-line treatment with ensartinib...

Ensartinib (X-396) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of ALK-positive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Although in vitro experiments and molecular docking suggested its potential as a CYP450 inhibitor, no further investigation or clinical trials have been conducted to assess its drug-drug interaction (DDI) risk. In this study, we conducted a series of in vitro experiments to elucidate the inhibition mechanism of ensartinib...

OBJECTIVE: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of different ALK-TKIs to guide clinical decision making. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Data were analyzed using random effects and consistency models under the frequency framework. RESULTS: Of 865 relevant studies, 13 RCTs (encompassing 3,353 patients) were finally included...

Non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) fusion showed promising responses to ALK tyrosine kinase inhibitors (TKIs). In this study, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next generation sequencing (NGS) and Sanger sequencing were performed to identify the presence of ALK fusion, to investigate whether the patient may benefit from TKI therapy. Postoperative pathological analysis indicated invasive adenocarcinoma with mainly mucinous type and partial micropapillary type in left lower lung...

ALK gene missense mutations are conventionally considered non-driver mutations without pathological significance, and therefore, there is a lack of effective target drugs against them. The standard treatment option for patients with ALK missense mutations is chemotherapy with or without antiangiogenic agents, which usually results in unsatisfactory outcomes. Herein, we present the case of a patient with metastatic lung adenocarcinoma harboring the only missense mutation in ALK D1225N responding to two ALK-tyrosine kinase inhibitors (TKIs), namely, crizotinib and ensartinib...

OBJECTIVE: To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK-positive non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK-positive NSCLC. METHODS: The effectiveness of ALKis was evaluated by assessing progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety...

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib...

BACKGROUND: The anaplastic lymphoma kinase (ALK) inhibitor treatment landscape is rapidly evolving, providing patients with ALK-positive (+) non-small cell lung cancer (NSCLC) with multiple therapy options, multiple lines of treatments, and prolonged survival. However, these recent treatment advances have resulted in additional increases in treatment costs. The objective of this article is to review the economic evidence of ALK inhibitors in patients with ALK+ NSCLC. METHODS: The systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) systematic reviews of economic evaluation...

ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management...

Anaplastic lymphoma kinase (ALK) rearrangements occur in ∼3%-6% of patients with advanced non-small-cell lung cancer (NSCLC). Small molecular drugs that effectively inhibit ALK gene have revolutionized the therapeutic paradigm for patients with ALK rearrangements, resulting in significant improvements in objective response rate, progression-free survival, and overall survival compared with classical platinum-based chemotherapy. Several ALK tyrosine kinase inhibitors (ALK-TKIs), including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib, have been recommended as standard first-line treatment for advanced NSCLC patients with ALK rearrangements...