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Journal of Chemotherapy (Florence,... Apr 2022Because of lacking of head-to-head comparison among lorlatinib, alectinib and brigatinib for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and... (Meta-Analysis)
Meta-Analysis
Comparison of lorlatinib, alectinib and brigatinib in ALK inhibitor-naive/untreated ALK-positive advanced non-small-cell lung cancer: a systematic review and network meta-analysis.
Because of lacking of head-to-head comparison among lorlatinib, alectinib and brigatinib for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced non-small-cell lung cancer (NSCLC), the optimal option for these patients still remains undefined. We searched published reports that described the activity and safety of those novel ALK inhibitors (lorlatinib, alectinib and brigatinib) for ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. Five randomized controlled trials were identified, covering 1111 subjects. In the network meta-analysis, lorlatinib seemed to prolong progression free survival than brigatinib (Hazard Ratio: 0.57, = 0.03) and alectinib (Hazard ratio: 0.65, = 0.05) for previously untreated patients with ALK-positive advanced NSCLC as assessed by the independent review committee. Meanwhile, lorlatinib significantly improved significant progression free survival than brigatinib (Hazard ratio: 0.57, = 0.03) and alectinib (Hazard ratio: 0.59, = 0.03) for ALK inhibitor-naive patients. Among lorlatinib, alectinib, brigatinib, and crizotinib, lorlatinib had the highest probability to reach the best overall confirmed response rates (probability of 48%) and intracranial confirmed response rates (probability of 44%). No significant difference was found among them in overall survival and adverse events analysis. In terms of progression free survival, our results indicated that lorlatinib was the best treatment choice for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. The future head-to-head trials assessing the relative efficacy of lorlatinib, alectinib and brigatinib were warranted.
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Carbazoles; Carcinoma, Non-Small-Cell Lung; Humans; Lactams; Lung Neoplasms; Network Meta-Analysis; Organophosphorus Compounds; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines
PubMed: 34139965
DOI: 10.1080/1120009X.2021.1937782 -
Sports Medicine (Auckland, N.Z.) Mar 2023Studies investigating the effects of common recovery modalities following acute strenuous exercise have reported mixed results. (Meta-Analysis)
Meta-Analysis
Effects of Cold-Water Immersion Compared with Other Recovery Modalities on Athletic Performance Following Acute Strenuous Exercise in Physically Active Participants: A Systematic Review, Meta-Analysis, and Meta-Regression.
BACKGROUND
Studies investigating the effects of common recovery modalities following acute strenuous exercise have reported mixed results.
OBJECTIVES
This systematic review with meta-analysis and meta-regression compared the effects of cold-water immersion (CWI) against other common recovery modalities on recovery of athletic performance, perceptual outcomes, and creatine kinase (CK) following acute strenuous exercise in physically active populations.
STUDY DESIGN
Systematic review, meta-analysis, and meta-regression.
METHODS
The MEDLINE, SPORTDiscus, Scopus, Web of Science, Cochrane Library, EmCare, and Embase databases were searched up until September 2022. Studies were included if they were peer reviewed, published in English, included participants who were involved in sport or deemed physically active, compared CWI with other recovery modalities following an acute bout of strenuous exercise, and included measures of performance, perceptual measures of recovery, or CK.
RESULTS
Twenty-eight studies were meta-analysed. CWI was superior to other recovery methods for recovering from muscle soreness, and similar to other methods for recovery of muscular power and flexibility. CWI was more effective than active recovery, contrast water therapy and warm-water immersion for most recovery outcomes. Air cryotherapy was significantly more effective than CWI for the promotion of recovery of muscular strength and the immediate recovery of muscular power (1-h post-exercise). Meta-regression revealed that water temperature and exposure duration were rarely exposure moderators.
CONCLUSION
CWI is effective for promoting recovery from acute strenuous exercise in physically active populations compared with other common recovery methods.
PROTOCOL REGISTRATION
Open Science Framework: https://doi.org/10.17605/OSF.IO/NGP7C.
Topics: Humans; Cold Temperature; Immersion; Myalgia; Water; Athletic Performance; Creatine Kinase
PubMed: 36527593
DOI: 10.1007/s40279-022-01800-1 -
Critical Reviews in Oncology/hematology Apr 2021Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence,... (Meta-Analysis)
Meta-Analysis Review
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are treatments commonly used for lung cancer. The toxicity profile including toxicity incidence, severity, and spectrum (involving various specific adverse events) of each EGFR-TKI are of particular clinical interest and importance. Data from phase II and III randomized controlled trials comparing treatments among EGFR-TKIs (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib) and chemotherapy for lung cancer were synthesized with Bayesian network meta-analysis. The primary outcome was systemic all-grade and grade ≥3 adverse events. The secondary outcome was specific all-grade adverse events including those of the skin, gastrointestinal tract, lung, etc. 40 trials randomizing 13,352 patients were included. Generally greater toxicity for dacomitinib and afatinib, and safety for icotinib were suggested. Furthermore, we found individual EGFR-TKIs had different toxicity spectrums. These findings provide a compelling safety reference for the individualized use of EGFR-TKIs for patients with lung cancer.
Topics: Bayes Theorem; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Network Meta-Analysis; Protein Kinase Inhibitors
PubMed: 33757838
DOI: 10.1016/j.critrevonc.2021.103305 -
Nature Reviews. Drug Discovery Aug 2020Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key mediator of cell death and inflammation. The unique hydrophobic pocket in the allosteric...
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key mediator of cell death and inflammation. The unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small-molecule inhibitors of its kinase activity, which have demonstrated safety in preclinical models and clinical trials. Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischaemic and acute conditions, such as sepsis, are emerging. This article reviews RIPK1 biology and disease-associated mutations in RIPK1 signalling pathways, highlighting clinical trials of RIPK1 inhibitors and potential strategies to mitigate development challenges.
Topics: Animals; Drug Delivery Systems; Humans; Mutation; Protein Kinase Inhibitors; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 32669658
DOI: 10.1038/s41573-020-0071-y -
Sports Medicine (Auckland, N.Z.) Jul 2022Studies investigating the effects of cold-water immersion (CWI) on the recovery of athletic performance, perceptual measures and creatine kinase (CK) have reported mixed... (Meta-Analysis)
Meta-Analysis
Impact of Cold-Water Immersion Compared with Passive Recovery Following a Single Bout of Strenuous Exercise on Athletic Performance in Physically Active Participants: A Systematic Review with Meta-analysis and Meta-regression.
BACKGROUND
Studies investigating the effects of cold-water immersion (CWI) on the recovery of athletic performance, perceptual measures and creatine kinase (CK) have reported mixed results in physically active populations.
OBJECTIVES
The purpose of this systematic review was to investigate the effects of CWI on recovery of athletic performance, perceptual measures and CK following an acute bout of exercise in physically active populations.
STUDY DESIGN
Systematic review with meta-analysis and meta-regression.
METHODS
A systematic search was conducted in September 2021 using Medline, SPORTDiscus, Scopus, Web of Science, Cochrane Library, EmCare and Embase databases. Studies were included if they were peer reviewed and published in English, included participants who were involved in sport or deemed physically active, compared CWI with passive recovery methods following an acute bout of strenuous exercise and included athletic performance, athlete perception and CK outcome measures. Studies were divided into two strenuous exercise subgroups: eccentric exercise and high-intensity exercise. Random effects meta-analyses were used to determine standardised mean differences (SMD) with 95% confidence intervals. Meta-regression analyses were completed with water temperature and exposure durations as continuous moderator variables.
RESULTS
Fifty-two studies were included in the meta-analyses. CWI improved the recovery of muscular power 24 h after eccentric exercise (SMD 0.34 [95% CI 0.06-0.62]) and after high-intensity exercise (SMD 0.22 [95% CI 0.004-0.43]), and reduced serum CK (SMD - 0.85 [95% CI - 1.61 to - 0.08]) 24 h after high-intensity exercise. CWI also improved muscle soreness (SMD - 0.89 [95% CI - 1.48 to - 0.29]) and perceived feelings of recovery (SMD 0.66 [95% CI 0.29-1.03]) 24 h after high-intensity exercise. There was no significant influence on the recovery of strength performance following either eccentric or high-intensity exercise. Meta-regression indicated that shorter time and lower temperatures were related to the largest beneficial effects on serum CK (duration and temperature dose effects) and endurance performance (duration dose effects only) after high-intensity exercise.
CONCLUSION
CWI was an effective recovery tool after high-intensity exercise, with positive outcomes occurring for muscular power, muscle soreness, CK, and perceived recovery 24 h after exercise. However, after eccentric exercise, CWI was only effective for positively influencing muscular power 24 h after exercise. Dose-response relationships emerged for positively influencing endurance performance and reducing serum CK, indicating that shorter durations and lower temperatures may improve the efficacy of CWI if used after high-intensity exercise.
FUNDING
Emma Moore is supported by a Research Training Program (Domestic) Scholarship from the Australian Commonwealth Department of Education and Training.
PROTOCOL REGISTRATION
Open Science Framework: 10.17605/OSF.IO/SRB9D.
Topics: Athletic Performance; Cold Temperature; Creatine Kinase; Humans; Immersion; Myalgia; Water
PubMed: 35157264
DOI: 10.1007/s40279-022-01644-9 -
Cancer Treatment Reviews Sep 2023The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the standard of care for hormone receptor-positive (HR + ) and human epidermal growth factor... (Meta-Analysis)
Meta-Analysis Review
The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the standard of care for hormone receptor-positive (HR + ) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, improving survival outcomes compared to endocrine therapy alone. Abemaciclib and ribociclib, in combination with endocrine therapy, have demonstrated significant benefits in invasive disease-free survival for high-risk HR+/HER2- early breast cancer patients. Each CDK4/6i-palbociclib, ribociclib, and abemaciclib-exhibits distinct toxicity profiles. Radiation therapy (RT) can be delivered with a palliative or ablative intent, particularly using stereotactic body radiation therapy for oligometastatic or oligoprogressive disease. However, pivotal randomized trials lack information on concomitant CDK4/6i and RT, and existing preclinical and clinical data on the potential combined toxicities are limited and conflicting. As part of a broader effort to establish international consensus recommendations for integrating RT and targeted agents in breast cancer treatment, we conducted a systematic review and meta-analysis to evaluate the safety profile of combining CDK4/6i with palliative and ablative RT in both metastatic and early breast cancer settings.
Topics: Humans; Female; Radiosurgery; Breast Neoplasms; Cyclin-Dependent Kinases; Cyclin-Dependent Kinase 4; Protein Kinase Inhibitors; Cyclin-Dependent Kinase 6; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37336117
DOI: 10.1016/j.ctrv.2023.102586 -
ESMO Open Dec 2022Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments'... (Review)
Review
BACKGROUND
Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available.
METHODS
We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib.
RESULTS
A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients.
CONCLUSIONS
Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.
Topics: Female; Humans; Aminopyridines; Breast Neoplasms; Cyclin-Dependent Kinase 4; Quality of Life; Cyclin-Dependent Kinase 6; Protein Kinase Inhibitors
PubMed: 36399953
DOI: 10.1016/j.esmoop.2022.100629 -
The Journal of Dermatological Treatment Feb 2022Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts on patients and is challenging to manage with limited treatment options. Recent studies have suggested promising results for JAK1/3 inhibitors including tofacitinib and ruxolitinib.
OBJECTIVE
To determine the expected response of vitiligo to JAK inhibitor therapy and factors which influence response rates.
METHODS
A systematic review and meta-analysis was performed according to PRISMA guidelines. Good response was defined as repigmentation >50% or a 'good' or 'excellent' outcome as described by authors. Partial response was defined as some repigmentation <50%.
RESULTS
From the 9 eligible studies, individual patient data from 45 cases were pooled. Good response was achieved in 57.8%, partial response in 22.2%, and none or minimal response in 20% of cases. When subgrouped according to site, facial vitiligo had the highest good response rate (70%), compared to extremities (27.3%) and torso/non-sun exposed areas (13.6%). Concurrent phototherapy was significant associated with higher rates of good overall response ( < .001) and good facial response ( < .001).
CONCLUSIONS
There is promising low-quality evidence regarding the effectiveness of JAK inhibitors in vitiligo. Concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; Phototherapy; Skin Pigmentation; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 32096671
DOI: 10.1080/09546634.2020.1735615 -
Cancer Treatment Reviews Mar 2020HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).
METHODS
A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins' I was used to quantify heterogeneity.
RESULTS
Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I = 33%), in HR+ (OR = 3.61, p < 0.001, I = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I = 0%) and in HR + disease (OR = 4.08, p = 0.001, I = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I = 0%).
CONCLUSIONS
The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Neoadjuvant Therapy; Neoplasm Staging; Receptor, ErbB-2; Remission Induction
PubMed: 32000054
DOI: 10.1016/j.ctrv.2020.101965 -
Neuro-oncology Jun 2021Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.
METHODS
Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models.
RESULTS
937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC.
CONCLUSION
There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
Topics: Brain Neoplasms; Breast Neoplasms; Female; Humans; Incidence; Receptor, ErbB-2; Triple Negative Breast Neoplasms
PubMed: 33367836
DOI: 10.1093/neuonc/noaa285