Efficacy and safety of first‐line treatments for patients with advanced anaplastic lymphoma kinase mutated, non–small cell cancer: A systematic review and network meta‐analysis

Yang, Pingting; Zhao, Qiang; Liao, Ziyi; Ma, Yingyin; Ma, Dong

doi:10.1002/cncr.34664

Cited by 8 publications

(2 citation statements)

References 75 publications

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“…ALK rearrangement was reported to be associated with a low response rate to immunotherapy ( 28 ). Advanced stage ALK-rearranged NSCLC patients treated with ALK-TKI reported superior progression-free survival (PFS) and objective response rates (ORRs) compared to those undergoing chemotherapy ( 29 , 30 ). A recent study analyzed the efficacy of adjuvant therapy in a cohort of 59 ALK-rearranged lung cancer patients and found that patients with adjuvant ALK-TKI demonstrated a better DFS and OS compared to those with chemotherapy ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center

Zeng,

Xiong,

Zhang

et al. 2024

Transl Lung Cancer Res

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Background Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) exhibited a higher propensity for lymph node metastasis (LNM). This study aimed to investigate risk factors of occult lymph node metastasis (OLNM) and recurrence in resectable ALK-rearranged NSCLC patients. Methods This retrospective analysis included patients with ALK-rearranged NSCLC receiving lung resections at Shanghai Pulmonary Hospital from June 2016 to August 2021. Logistic regression analysis was used to ascertain predictors of OLNM, and Cox regression analysis to identify risk factors of recurrence. Results A total of 603 resectable ALK-rearranged NSCLC patients were included. The mean age was 55 years old. There were 171 patients (28.4%) pathologically confirmed to have LNM, 51.5% of which were occult. Logistic regression analysis identified clinical tumor size and computed tomography (CT) density as independent factors for OLNM. Cox regression analysis showed that pleural invasion and pathological tumor size were independent prognosticators for recurrence in pathologically nodal negative patients. Among pathologically nodal positive patients, adjuvant ALK-tyrosine kinase inhibitors (TKI) showed a similar recurrence-free survival (RFS) to chemotherapy (hazard ratio, 0.454; 95% confidence interval, 0.111–1.864). Conclusions Assessing the potential risk of OLNM is required for ALK-rearranged NSCLC patients with large tumors characterized by high CT densities. Patients with large pathological tumor size or pleural infiltration should be closely monitored despite being pathologically nodal negative. Additionally, adjuvant ALK-TKI may present a comparable RFS to chemotherapy in pathologically nodal positive patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center

Zeng,

Xiong,

Zhang

et al. 2024

Transl Lung Cancer Res

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“…Brigatinib shows results similar to the III-generation TKI [ 28 ] and has a less favorable adverse event profile in comparison to crizotinib, with a frequency of 73% vs. 61% of grade 3 complications [ 188 ]. 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 ].…”

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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Metastatic brain tumors: from development to cutting‐edge treatment

Tanzhu,

Chen,

Ning

et al. 2024

MedComm

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Metastatic brain tumors, also called brain metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the brain include lung cancer and breast cancer. In recent years, the prognosis for BM patients has improved, and significant advancements have been made in both clinical and preclinical research. This review focuses on BM originating from lung cancer and breast cancer. We briefly overview the history and epidemiology of BM, as well as the current diagnostic and treatment paradigms. Additionally, we summarize multiomics evidence on the mechanisms of tumor occurrence and development in the era of artificial intelligence and discuss the role of the tumor microenvironment. Preclinically, we introduce the establishment of BM models, detailed molecular mechanisms, and cutting‐edge treatment methods. BM is primarily treated with a comprehensive approach, including local treatments such as surgery and radiotherapy. For lung cancer, targeted therapy and immunotherapy have shown efficacy, while in breast cancer, monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates are effective in BM. Multiomics approaches assist in clinical diagnosis and treatment, revealing the complex mechanisms of BM. Moreover, preclinical agents often need to cross the blood–brain barrier to achieve high intracranial concentrations, including small‐molecule inhibitors, nanoparticles, and peptide drugs. Addressing BM is imperative.

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Efficacy and safety of first‐line treatments for patients with advanced anaplastic lymphoma kinase mutated, non–small cell cancer: A systematic review and network meta‐analysis

Cited by 8 publications

References 75 publications

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center

Prognostic factors of resectable anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) patients: a retrospective analysis based on a single center

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

Metastatic brain tumors: from development to cutting‐edge treatment

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