- |||||||||| Review, Journal: An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance. (Pubmed Central) - Feb 23, 2022
Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown.
- |||||||||| Alecensa (alectinib) / Roche
A Case of ALK Positive Adenocarcinoma of Unknown Primary with Good Response to Alectinib (Area D, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_3309; No new metastatic lesions were noted and there was no evidence of primary neoplasm in the chest. Positive ALK rearrangement in patients with CUP provides a target for ALK-inhibiting agents such as alectinib with beneficial outcomes similar to treatment of primary ALK-positive non-small cell lung cancer.
- |||||||||| Genomic Determinants of Brain Metastases in ALK+ Non-Small Cell Lung Cancer ([VIRTUAL]) - Feb 12, 2022 - Abstract #IASLCTTLC2022IASLC_TTLC_162;
We identify CDKN2A/2B loss as a genomic feature potentially conferring an increased risk in the development of brain metastases in ALK+ NSCLC. Validation in larger cohorts (ideally with prospective longitudinal brain surveillance) is warranted, particularly to increase our ability to detect differences among ALK fusion variants.
- |||||||||| Ninlaro (ixazomib) / Takeda, Alecensa (alectinib) / Roche
Journal: Proteasome inhibition overcomes ALK-TKI resistance in ALK-rearranged/TP53 mutant NSCLC via Noxa expression. (Pubmed Central) - Feb 11, 2022 In subcutaneous tumor models, combination of ixazomib and alectinib prominently induced tumor regression and apoptosis even though the tumors were generated from ALK-rearranged NSCLC cells with non-functional p53. Conclusions:These clinical and preclinical results indicate concomitant TP53 mutations reduce the efficacy of alectinib for ALK-rearranged NSCLC and the combined use of a proteasome inhibitor with alectinib is a promising therapy for ALK-rearranged/TP53-mutated NSCLC.
- |||||||||| Alunbrig (brigatinib) / Takeda
PK/PD data, Journal: Effect of severe renal impairment on the pharmacokinetics of brigatinib. (Pubmed Central) - Feb 3, 2022 Unbound brigatinib exposure (area under the plasma concentration-time curve from time zero to infinity) was approximately 92 % higher in patients with severe renal impairment compared with healthy volunteers with normal renal function. The renal clearance of brigatinib in patients with severe renal impairment was approximately 20 % of that observed in volunteers with normal renal function. Conclusions These findings support a brigatinib dosage reduction of approximately 50 % in patients with severe renal impairment.Trial registry: Not applicable.
- |||||||||| Journal: Recommendations from Experts in the Management of Adverse Reactions to ALK Inhibitors (2021 Version) (Pubmed Central) - Feb 3, 2022
However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions..
- |||||||||| Alecensa (alectinib) / Roche
Clinical, Journal: ALK-rearranged histiocytosis: report of two cases with involvement of the central nervous system. (Pubmed Central) - Jan 29, 2022 Clinical presentation and patient outcome vary greatly, ranging from mild to life-threatening diseases. Rare cases of histiocytosis harbouring ALK rearrangements, mainly with KIF5B as fusion partner, have been recently reported (1-9), with disease involvement of central nervous system (CNS) described only in occasional cases, as a part of a systemic disease or, exceptionally, as the unique manifestation of the disease.
- |||||||||| Review, Journal: Targetable gene fusions and aberrations in genitourinary oncology. (Pubmed Central) - Jan 28, 2022
Erdafitinib has been tested for the treatment of FGFR-rearranged bladder cancer. Other anti-fibroblast growth factor receptor 3 (FGFR3) compounds are showing promising results in the treatment of bladder cancer, including infigratinib and pemigatinib, and all are currently in clinical trials.
- |||||||||| Xalkori (crizotinib) / Pfizer, Tagrisso (osimertinib) / AstraZeneca, Alecensa (alectinib) / Roche
Journal: Development and validation of an HPLC-MS/MS method to simultaneously quantify alectinib, crizotinib, erlotinib, gefitinib and osimertinib in human plasma samples, using one assay run. (Pubmed Central) - Jan 27, 2022 Alectinib, crizotinib, erlotinib and gefitinib were all stable for at least 4 hours in whole blood (at room temperature (RT) and at 4°C) and for at least one month in EDTA-plasma when stored at -80°C, while osimertinib proved to be unstable at RT. Although high-performance liquid chromatography was used, the run time was short and comparable with other methods using ultra-high performance liquid chromatography.
- |||||||||| Alecensa (alectinib) / Roche
Journal: Sensitivity of eight types of ALK fusion variant to alectinib in ALK-transformed cells. (Pubmed Central) - Jan 27, 2022 There was no significant difference in the IC50 values between cells, with a <3.6-fold difference in responsiveness. In conclusion, these eight ALK variants had similar sensitivity to alectinib in vitro, indicating that it may not be possible to predict the response to alectinib just by determination of the ALK variant type in ALK fusion-positive NSCLCs.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Alecensa (alectinib) / Roche
Lorlatinib Induces Rapid Response in Chemotherapy-Refractory and Alectinib-Refractory Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma. (Salt Palace Convention Center Hall A) - Jan 9, 2022 - Abstract #TCTASTCTCIBMTR2022TCT_ASTCT_CIBMTR_1280; One cycle of dexamethasone, cisplatin, high dose cytarabine [DHAP] with alectinib achieved a complete metabolic response on 18 F-FDG PET/CT with a normal spleen...Then a fludarabine melphalan matched unrelated donor allogeneic peripheral blood stem cell transplant achieved full donor chimerism without lymphoma on day +30 bone marrow biopsy...Clathrin-ALK is required for tumor maintenance. ALK could be the optimal target for the therapy of ALK+LBCL.
- |||||||||| Alecensa (alectinib) / Roche
Journal: Revisiting a lower starting dose of alectinib in ALK-Positive non-small cell lung cancer. (Pubmed Central) - Jan 4, 2022 Randomized trials have shown that the 600 mg dose is associated with more grade ≥3 adverse events and more changes in treatment in contrast to the 300 mg dose. A lower dose of Alectinib may limit treatment disruptions and dose reductions particularly for specific patient populations-particularly those with a lower body weight.
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