Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis

Tao, Yunxia; Zhou, Yu; Tang, Le; Chen, Haizhu; Feng, Yu; Shi, Yuankai

doi:10.1007/s10637-022-01242-6

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…Although structural and pharmacokinetic features of brigatinib are well described [14,15], it remains un-clear whether those differences may have any impact on the lower risk of brigatinib-induced hepatotoxicity in comparison with other ALKi [16]. Alterations in creatine kinase (CK) are recognized as common adverse events in patients treated with ALKi for solid tumors [17].…”

Section: Discussionmentioning

confidence: 99%

Replacement of ALK inhibitors as an effective strategy for reducing drug toxicity in non-small cell lung cancer patients with ALK gene rearrangement

et al. 2023

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This case report examines the effects of replacement of anaplastic lymphoma kinase inhibitor (ALKi) as a strategy to reduce drug toxicity in patients with non-small cell lung cancer (NSCLC) with ALK gene rearrangements. A 61-year-old female patient with lung adenocarcinoma encountered difficulties in ALK abnormalities diagnosis: the expression of abnormal ALK protein was not detected by the immunohistochemistry (IHC) assay, but ALK gene rearrangement was present in next generation sequencing (NGS) and fluorescence in situ hybridization (FISH) assays. The patient was initially treated with second-generation ALKi (alectinib). However, the patient experienced severe hepatotoxicity. She was successfully switched to brigatinib (another second-generation ALK inhibitor). During brigatinib therapy, a transient increase in creatinine kinase concentration was observed, which required brigatinib dose reduction. Effectiveness of both anti-ALK agents was observed (partial response to treatment, followed by disease stabilization). This case report illustrates the difficulties in diagnosing ALK gene rearrangements and the possibility of replacing ALK inhibitors without compromising treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Replacement of ALK inhibitors as an effective strategy for reducing drug toxicity in non-small cell lung cancer patients with ALK gene rearrangement

et al. 2023

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“…[10][11][12] First of all, both targeted therapy and immunotherapy have many corresponding side effects, such as hand-foot syndrome, hypertension, proteinuria, immune pneumonia, immune hepatitis, and so forth. 10,13,14 Besides, many tumor-targeted therapies are prone to drug resistance, and immunotherapy has no therapeutic response to many immune cold tumors. 15,16 So, it's very important to develop more effective treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Although the current treatment of tumors is progressing fast and targeted therapy and immunotherapy have greatly improved the prognosis of tumors, there are many shortcomings in these treatments 10–12 . First of all, both targeted therapy and immunotherapy have many corresponding side effects, such as hand‐foot syndrome, hypertension, proteinuria, immune pneumonia, immune hepatitis, and so forth 10,13,14 . Besides, many tumor‐targeted therapies are prone to drug resistance, and immunotherapy has no therapeutic response to many immune cold tumors 15,16 .…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel tumor necrosis factor‐related apoptosis‐inducing ligand mutant MuR5S4‐TR

Zhao

Liu

et al. 2023

Asia-Pac J Clncl Oncology

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AimTumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) can selectively kill tumor cells but has no significant effect on normal cells. However, the use of TRAIL is limited for resistance by more than 50% of the tumor cell lines. It's very important to develop a more efficient form of TRAIL for cancer treatment.MethodsThe N‐terminal in soluble fragments (114–281aa) of TRAIL was redesigned to construct a novel TRAIL mutant‐MuR5S4‐TR. The Cell Counting Kit‐8 method to explore the antitumor effects. The potential mechanisms were also explored.ResultsNovel TRAIL mutant with cell‐penetrating peptides (CPP) like and Second mitochondria‐derived activator of caspases (Smac) like structure‐MuR5S4‐TR was successfully constructed. The prokaryotic expression system was successfully built, and the MuR5S4‐TR was purified and reconfirmed by western blot. MuR5S4‐TR could enhance the antitumor effects of TRAIL in most of the cancer cell lines significantly, NCI‐H460 lung cancer cell line, for instance. After MuR5S4‐TR treatment, the expressions of death receptor 4 (DR4), DR5, Caspase‐8, and cleaved Caspase‐3 were remarkably increased, however, there was no significant difference in X‐linked inhibitor of apoptosis expression.ConclusionWe constructed a novel TRAIL mutant with CPP‐like and Smac‐like structure‐MuR5S4‐TR. The MuR5S4‐TR showed significantly stronger antitumor effects than TRAIL in many tumor cell lines. The MuR5S4‐TR showed strong antitumor effects both in vitro and in vivo. This preliminary study implies that MuR5S4‐TR may be a more efficient form of TRAIL for cancer therapy.

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“…Alectinib was the only ALK inhibitor to show a safety benefit over crizotinib, with a frequency of grade 3 events of 45% vs. 51% [ 189 ]. Lorlatinib seems to be safer than ceritinib [ 190 , 191 ]. Compared to pemetrexed-based chemotherapy, lorlatinib shows an unfavorable toxicity profile since pemetrexed was responsible for no dose interruption or de-escalation, and a minor rate of grade 3 events occurred (14% vs. 38%).…”

Section: Safety Profile and Clinical Managementmentioning

confidence: 99%

From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC)

Fabbri,

Di Federico,

Astore

et al. 2023

Diagnostics

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Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses.

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Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis

Cited by 7 publications

References 46 publications

Replacement of ALK inhibitors as an effective strategy for reducing drug toxicity in non-small cell lung cancer patients with ALK gene rearrangement

Replacement of ALK inhibitors as an effective strategy for reducing drug toxicity in non-small cell lung cancer patients with ALK gene rearrangement

Construction and validation of a novel tumor necrosis factor‐related apoptosis‐inducing ligand mutant MuR5S4‐TR

From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC)

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