Clinical Impact of Switching to Ceritinib After Severe AEs Related to Crizotinib/Alectinib in a Novel PTH2R-ALK Fusion Lung Adenocarcinoma: A Case Report

Lung cancer is still the leading cause of morbidity and mortality by cancer among men, according to the latest epidemiological data in China. Anaplastic lymphoma kinase (ALK) rearrangements act as key oncogenic drivers of non-small cell lung cancer (NSCLC) and have been identified in 5– 6% of NSCLC. Although ALK inhibitors (ALK-TKIs) were proven to be more effective than chemotherapy in ALK-positive NSCLC patients and the safety profile of these drugs was favorable, novel ALK fusions NSCLC might discontinue or switch treatment because of adverse events (AEs) have rarely previously been reported. Here, we describe a male patient with stage IV lung adenocarcinoma who carried a novel PTH2R-ALK fusion identified by next-generation sequencing (NGS). The patient first took crizotinib but switched to alectinib due to gastrointestinal AEs. Although alectinib remained effective on tumors, ceritinib (450 mg) was replaced after the AEs of hyperbilirubinemia occurred. After reducing the dose to 30..... READ ARTICLE

OncoTargets and Therapies DOI:10.2147/OTT.S340984

Authors: Shen G, Du Y, Shen J, Zhang J, Xia X, Huang M and Shen W.

Case Study, group1Kirk SmithDecember 9, 2021PTH2R-ALK, non-small cell lung cancer, ceritinib, adverse events

Immune checkpoint inhibitors in oncogene-addicted non-small cell lung cancer: a systematic review and meta-analysis

Eighty-seven studies were included in the qualitative analysis. EGFR mutation may be a biomarker of poor response to single-agent ICIs (7% of EGFR-mutant NSCLC patients achieved disease response in prospective trials), while encouraging results have been shown with combination strategies. KRAS-mutated disease (response rate, RR, 22%) has different clinical and pathological characteristics, and the co-existence of additional mutations (e.g., STK11 or TP53) influence tumor microenvironment and response to immunotherapy. Other molecular alterations have been marginally considered prospectively, and data from clinical practice are variegated, given poor effectiveness of ICIs in ALK-rearranged disease (RR 9.5%, pooling the data of retrospective studies) or some encouraging results in BRAF-(RR 25%, retrospective data) or MET-driven one (with estimations conditioned by the presence of both exon 14 skipping mutations and gene amplification in reported series). In oncogene-addicted NSCLC (with ..... READ ARTICLE

Translational lung Cancer Research DOI:10.21037/tlcr-20-941

Authors: Giorgia Guaitoli, Marcello Tiseo, Massimo Di Maio, Luc Friboulet and Francesco Facchinetti

Retrospective Real-World Outcomes for Patients With ALK-Rearranged Lung Cancer Receiving ALK Receptor Tyrosine Kinase Inhibitors

Clinical trials have firmly established that ALK TKIs are safe, well tolerated, and effective; these findings reveal that their impact in a real-world setting is just as profound. The availability and use of ALK TKI therapies contribute to the impressive gains in survival experienced by contemporary patients with ALK-rearranged disease, rendering patients with this oncodriven form of NSCLC among the longest surviving patients with lung cancer. READ ARTICLE

Journal of Thoracic Oncology, Clinical and Research Reports DOI:10.1016/j.jtocrr.2021.100157

Authors: Amanda J. W. Gibson, Adrian Box, Michelle L. Dean, Anifat A. Elegbede, Desiree Hao, Randeep Sangha, D. Gwyn Bebb

Real-World OutcomesKirk SmithApril 1, 2021ALK, NSCLC, Targeted therapy, adverse events

Efficacy and safety of ceritinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer: A systematic review and meta-analysis

What is known and objective: Ceritinib is a new, oral, potent and selective second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration of the United States in April 2014. It is active in crizotinib-re-sistant patients, especially in patients with non-small cell lung cancer (NSCLC) and brain metastasis. The aim of this study was to analyse the effects and side effects of ceritinib in ALK-rearranged NSCLC.Methods: We searched articles published from January 1980 to March 2019 in PubMed, EMBASE, Cochrane Library and Web of Science. The pooled estimate and 95% CI were calculated with DerSimonian-Laird method and the random effect model.Results and discussion: From 15 articles, 2,598 patients were included in the meta-analysis. Eleven studies reported the ORR, and the DCR was presented in 10 stud-ies. The ORR and DCR of ceritinib were 0.48 (95% CI, 0.39-0.57) and 0.76 (95% CI, 0.69-0.82), respectively. The PFS and OS were presented in nine and ..... READ ARTICLE

Journal of Clinical Pharmacy and Therapeutics DOI:10.1111/jcpt.13157

Authors: Wei Tian, Ping Zhang, Yuan Yuan, Xiao-Hui Deng, Rui Yue, Xiao-Zhu Ge

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Background: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. Patients and Methods: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. Results: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively. Conclusion: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC. READ ARTICLE

In Vivo DOI:10.21873/invivo.11767

Authors: TAKAAKI NAKASHIMA, TAKESHI NONOSHITA, HIDENARI HIRATA, KOUJI INOUE, AKIRA NAGASHIMA, TADAMASA YOSHITAKE, KAORI ASAI and YOSHIYUKI SHIOYAMA

Case StudyKirk SmithJanuary 1, 2020ALK-TKI, radio therapy, adverse events, lung adenocarcinoma, brain metastases