Tyrosine Research
40 peer-reviewed studies · Evidence score: 7/10
Infectious complications in CLL/SLL patients receiving Bruton's Tyrosine Kinase inhibitors - systematic review and meta-analysis of randomized controlled trials
Buchrits S et al. • Annals of hematology (2025)
This meta-analysis examined the effects of Tyrosine.
- Pooled risk ratios (RR) with 95% confidence intervals (CIs) were estimated using fixed or random effects models based on heterogeneity.
- Similarly, BTKi monotherapy was not associated with an increased risk of grade 3-4 infections [RR 1.05 (95% CI: 0.76-1.44, I2 = 61%), 5 trials].
- The risk of sepsis was not significantly increased with BTKi regimens [BTKi + anti-CD20: RR 0.48 (95% CI: 0.12-1.84, I2 = 69%), 4 trials; BTKi monotherapy: RR 0.50 (95% CI: 0.25-1.01, I2 = 0%), 5 trials].
Efficacy of therapies for intermediate-stage hepatocellular carcinoma: systematic review and network meta-analysis
Zong S et al. • Frontiers in immunology (2025)
Seven therapies showed better efficacy than TACE alone for particular patients with intermediate-stage HCC.
- Seven therapies showed better efficacy than TACE alone for particular patients with intermediate-stage HCC.
- Published in Frontiers in immunology (2025)
- Further research warranted to confirm findings
Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: systematic review and network meta-analysis
Ma Z et al. • BMJ (Clinical research ed.) (2025)
In patients with EGFR-mutated NSCLC, first and third generation EGFR tyrosine kinase inhibitors, as well as combination therapies with antiangiogenesis, were associated with increased risks of cardiovascular adverse events.
- Compared with placebo, both first generation (odds ratio 1.51, 95% confidence interval 1.01 to 2.26; high certainty; pooled incidence 3.2%) and third generation EGFR tyrosine kinase inhibitors (2.18, 1.46 to 3.27; high certainty; 9.5%) were associated with increased risks of cardiac adverse events.
- Among third generation inhibitors, osimertinib (2.53, 1.53 to 4.19; high certainty; 8.9%) and lazertinib (2.84, 1.17 to 6.91; moderate certainty; 2.7%) were associated with cardiac adverse events.
- Also, the risk of arrhythmias was significantly higher with third generation inhibitors (3.26, 1.83 to 5.81; high certainty; 7.3%), such as osimertinib alone (3.35, 1.75 to 6.40; high certainty; 6.2%) and in combination with antiangiogenesis.
Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis
Zhao Y et al. • The Lancet. Oncology (2024)
For individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs, ICI-antiangio-chemo was identified as the optimal treatment option.
- For individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs, ICI-antiangio-chemo was identified as the optimal treatment option.
- The toxicity of this treatment was acceptable but needs careful attention.
- ICI-chemo showed appreciably greater efficacy than the standard-of-care chemotherapy.
What is the optimal first-line regimen for advanced non-small cell lung cancer patients with epidermal growth factor receptor mutation: a systematic review and network meta-analysis
Zhang W et al. • BMC pulmonary medicine (2024)
Our study concluded that combination regimens based on third-generation TKIs (osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced non-small cell lung cancer.
- In terms of safety profile, combination therapies based on third-generation TKIs did not significantly increase the incidence of grade 3 or higher adverse events compared with other regimens.
- Published in BMC pulmonary medicine (2024)
- Further research warranted to confirm findings
Bruton tyrosine kinase inhibitor monotherapy in B-cell lymphoma and risk of infection: A systematic review and meta-analysis of randomized controlled trials
Zuber M et al. • Hematological oncology (2024)
Hematological Oncology published by John Wiley & Sons Ltd.
- The overall pooled RR for any grade upper respiratory tract infections (URTI) associated with BTK inhibitor treatment was 1.55 (95% Confidence Interval (CI) 1.22-1.97).
- The RR of grade ≥3 URTI was reported in 14 out of 1046 patients, yielding an RR of 1.46 (95% CI 0.61-3.54), which was not statistically significant.
- The pooled RR of any grade pneumonia was 1.20 (95% CI 0.68-2.10) and grade ≥3 pneumonia was 1.12 (95% CI 0.67-1.85), both of which were not statistically significant.
Adverse Event Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-small Cell Lung Cancer: An Updated Meta-analysis
Zhou S et al. • Targeted oncology (2024)
Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs.
- Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs.
- Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.
- Further research warranted to confirm findings
The Impact of Concomitant Medications on the Overall Survival of Patients Treated with Systemic Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-analysis
Tsuboi I et al. • Clinical genitourinary cancer (2024)
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- Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001).
- Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively).
- In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02).
Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis
Luo Y et al. • Lung cancer (Amsterdam, Netherlands) (2023)
The toxicity spectra of ALK-TKIs differed.
- The rates of grade 3-4 AEs were: alectinib (16.2%), crizotinib (46.4%), brigatinib (63.7%), ensartinib (75.6%), ceritinib (78.3%), and lorlatinib (91.6%).
- The toxicity spectra of ALK-TKIs differed.
- Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.
Efficacy and Safety of Bruton Tyrosine Kinase Inhibitor Plus Anti-CD20 Antibody Therapy Compared With Chemoimmunotherapy as Front-line Treatment for Chronic Lymphocytic Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Nguyen TT et al. • Journal of immunotherapy (Hagerstown, Md. : 1997) (2023)
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- BTKi + anti-CD20 antibody treatment significantly prolonged PFS [hazard ratio (HR), 0.25; 95% confidence interval (CI), 0.15-0.42] compared with CIT, while the combination therapy did not significantly improve OS compared with CIT (HR, 0.73; 95% CI, 0.50-1.06).
- Although pooled analysis indicated that the addition of BTKi to anti-CD20 antibody led to a higher ORR than CIT [risk ratio (RR), 1.16; 95% CI, 1.13-1.20], there was no difference in CR between the two arms (RR, 1.10; 95% CI, 0.27-4.55).
- The risk of grade ≥3 adverse effects (AE) was comparable between the two groups (RR, 1.04; 95% CI, 0.92-1.17).
Ibrutinib-associated dermatologic toxicities: A systematic review and meta-analysis
Nocco S et al. • Critical reviews in oncology/hematology (2022)
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- The incidence of high-grade toxicities included mucocutaneous infection (1.3%; 95%CI, 0.5-2.2%), rash (0.1%; 95%CI, 0.0-0.2%), mucositis (0.1%; 95%CI, 0.0-0.3%), and edema (0.1%; 95%CI, 0.0-0.2%).
- It is imperative that clinicians familiarize themselves with ibrutinib-associated dermatologic toxicities to learn how to manage them, prevent discontinuation, and improve patient outcomes.Copyright © 2022 Elsevier B.V.
- All rights reserved.
Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002-2020)
Haber PK et al. • Gastroenterology (2021)
Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results.
- Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results.
- A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.
- Further research warranted to confirm findings
First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis
Vener C et al. • Blood advances (2020)
This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.© 2020 by The American Society of Hematology.
- Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS.
- GRADE showed that the certainty of the evidence ranged from high to moderate.
- This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.© 2020 by The American Society of Hematology.
Safety and efficacy of addition of VEGFR and EGFR-family oral small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: a systematic review and meta-analysis of randomized controlled trials
Funakoshi T et al. • Cancer treatment reviews (2014)
It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.
- Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36).
- The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03).
- It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.
Metabolomics on depression: A comparison of clinical and animal research
Wang Y et al. • Journal of affective disorders (2024)
This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
- This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
- Published in Journal of affective disorders (2024)
- Further research warranted to confirm findings
Lithium and disease modification: A systematic review and meta-analysis in Alzheimer's and Parkinson's disease
Singulani MP et al. • Ageing research reviews (2024)
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- Lithium treatment reduced amyloid-β and tau levels and significantly improved cognitive behavior in animal models of AD.
- Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model.
- Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients.
Diagnostic capacity of sFlt-1/PlGF ratio in fetal growth restriction: A systematic review and meta-analysis
Chen W et al. • Placenta (2022)
The pooled sensitivity, specificity, and AUC for the sFlt-1/PlGF ratio ≥85 group were 0.79 (95% CI = 0.66-0.89), 0.69 (95% CI = 0.65-0.74), and 0.8197, respectively.
- A sFlt-1/PlGF ratio >33 was demonstrated a predictive value for FGR with a pooled sensitivity of [0.63, 95% confidence interval (CI) = 0.54-0.71], specificity of (0.84, 95% CI = 0.83-0.85), and area under the curve (AUC) of 0.8354.
- The pooled sensitivity, specificity, and AUC for the sFlt-1/PlGF ratio ≥85 group were 0.79 (95% CI = 0.66-0.89), 0.69 (95% CI = 0.65-0.74), and 0.8197, respectively.
- Further research warranted to confirm findings
Correlation between ALK+ non-small cell lung cancer targeted therapy and thrombosis: a systematic review and network meta-analysis
Qi Y et al. • BMJ open (2024)
Compared with chemotherapy, alectinib, lorlatinib, brigatinib and ceritinib, crizotinib significantly increased the risk of TE and VTE.
- Analysis of eight RCTs showed that, compared with that for crizotinib, there was a lower risk of total TE with chemotherapy (OR, 0.28; 95% credible intervals (CrI) 0.11 to 0.63), brigatinib (OR 0.31; 95% CrI 0.11 to 0.79) and ceritinib (OR 0.13; 95% CrI 0.03 to 0.45).
- In addition, analysis of venous TE (VTE) showed similar results, with a lower occurrence for chemotherapy (OR 0.27; 95% CrI 0.1 to 0.62), brigatinib (OR 0.18; 95% CrI 0.04 to 0.6) and ceritinib (OR 0.1; 95% CrI 0.02 to 0.43) compared with that for crizotinib.
- Compared with chemotherapy, alectinib, lorlatinib, brigatinib and ceritinib, crizotinib significantly increased the risk of TE and VTE.
Tyrosine supplementation for phenylketonuria
Remmington T et al. • The Cochrane database of systematic reviews (2021)
From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice.
- The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05).
- From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice.
- Further randomised controlled studies are required to provide more evidence.
Systematic review and network meta-analysis of lorlatinib with comparison to other anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) as first-line treatment for ALK-positive advanced non-smallcell lung cancer (NSCLC)
Ou SH et al. • Lung cancer (Amsterdam, Netherlands) (2024)
Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs.
- The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib.
- Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs.
- Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs.