Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent EGFR mutations and DCTN1-ALK fusion

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions ..... READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14291

Authors: Shuyuan Wang, Bo Yan, Yanwei Zhang, Jianlin Xu, Rong Qiao, Yu Dong, Bo Zhang, Yiming Zhao, Lele Zhang, Jie Qian, Jun Lu, Ruiying Zhao, Baohui Han

Case Study, group1Kirk SmithDecember 28, 2021alectinib, osimertinib, brain metastasis, ALK, lung, EGFR, DCTN1-ALK

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases

Purpose: The performance of alectinib and crizotinib in untreated anaplastic lymphoma kinase (ALK)-positive patients with non-small-cell lung cancer (NSCLC) and symptomatic and synchronic brain metastases is largely unknown. This retrospective study assessed the effectiveness of alectinib and crizotinib, together with intracranial therapies in a cohort of these patients.
Patients and Methods: This study included 34 previously untreated ALK-positive NSCLC patients with three or fewer intracranial metastases. Of these patients, 13 received oral alectinib 600 mg twice daily, and 21 received oral crizotinib 250 mg twice daily, until progressive disease, unacceptable toxicity, or death. All intracranial metastases were treated with craniotomy, CyberKnife, or both.
Results: Median overall progression-free survival (PFS) was 32.8 months (95% CI 24.4– 41.2 months) in patients treated with alectinib and 8.0 months (95% CI 7.3– 8.7 months) in patients treated with crizotinib. Median PFS of brain..... READ ARTICLE

Onco Targets Therapy DOI:10.2147/OTT.S345439

Authors: Yin Q, Li P, Wang P, Zhang Z, Liu Q, Sun Z, Li W, Ma L, Wang X

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase‐positive non‐small cell lung cancer with triple problems

Alectinib treatment is effective in patients with anaplastic lymphoma kinase (ALK) gene rearrangement‐positive non‐small cell lung cancer (NSCLC; hereafter ALK‐positive NSCLC) who exhibit central nervous system (CNS) relapse and poor performance status (PS). Lorlatinib treatment is effective upon failure of other ALK inhibitor‐based treatments. However, much remains unknown about the efficacy of lorlatinib in patients with ALK‐positive NSCLC, who have triple problems, carcinomatous meningitis, poor PS, and dysphagia, after alectinib treatment. Here, we report the remarkable response of a 73‐year‐old patient with ALK‐positive NSCLC showing carcinomatous meningitis due to CNS metastases, poor PS, and dysphagia to lorlatinib. Lorlatinib administration through a nasogastric tube alleviated complications related to consciousness within three days, and the patient survived for 16 months after CNS relapse. Lorlatinib could be a treatment option for patients with ALK‐positive NSCLC showing carcinomatous meningitis, poor PS, and dysphagia upon failure of other ALK inhibitor‐based treatments. READ ARTICLE

Respiratory Case Reports DOI:10.1002/rcr2.796

Authors: Kota Sasaki, Yusuke Yokota, Toshihito Isojima, Mayumi Fujii, Kengo Hasui, Yu Chen, Kensuke Saito, Takenori Takahata, Seiko Kindaichi, and Atsushi Sato

Efficacy and safety of crizotinib plus bevacizumab in ALK/ROS-1/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study

This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive ALK rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in ALK/ROS-1/c-MET positive NSCLC patients. READ ARTICLE

American Journal of Translational Research DOI:10.1016/j.cllc.2021.06.011

Authors: Huang Z., Xiong Q., Cui Z., Tao H., Zhang S., Wang L., Cui P., Chen S., Huang D., Yang B., Hu Y.

Clinical TrialsKirk SmithMarch 15, 2021crizotinib, bevacizumab, ALK, ROS-1, c-MET, brain metastasis