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Bioscience Reports Jan 2020Jinlong capsule (JLC), a type of herbal medicine, is considered to be a promising adjuvant therapy for hepatocellular carcinoma (HC). Although an analysis of the... (Meta-Analysis)
Meta-Analysis
Jinlong capsule (JLC), a type of herbal medicine, is considered to be a promising adjuvant therapy for hepatocellular carcinoma (HC). Although an analysis of the published literature has been performed, the exact effects and safety of JLC are yet to be systematically investigated. Therefore, a wide-ranging systematic search of electronic databases to draw conclusions was performed. Data from 29 trials, including 2488 patients with advanced HC, were analyzed. The results indicated that, compared with conventional treatment alone, the combination of conventional treatment and JLC markedly improved overall patient response (odds ratio (OR) 2.06 [95% confidence interval (CI) 1.71-2.49]; P<0.00001), disease control rate (DCR) (OR 2.17 [95% CI 1.74-2.71]; P<0.00001) and quality of life (QoL) (OR 2.71 [95% CI 2.05-3.58]; P<0.00001), and significantly prolonged 6- (P=0.01), 12- (P<0.00001), 24- (P=0.001) and 36-month (P<0.0001) overall survival (OS) rates. The immune function of patients was also significantly enhanced after combined conventional therapy and JLC treatment, indicated by clearly increased percentages of CD3+ (P<0.0001), CD4+ (P<0.00001) and natural killer (NK) cells (P=0.0003), and CD4+/CD8+ ratio (P<0.00001). The incidence of leukopenia (P<0.00001), hepatotoxicity (P=0.005), and myelosuppression (P=0.0007) was lower in HC patients injected with JLC, whereas other adverse events did not differ significantly between the two groups (P>0.05). In summary, results of this meta-analysis suggest that the combination of conventional treatment and JLC is more effective for the treatment of HC than conventional treatment alone.
Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Hepatocellular; Drugs, Chinese Herbal; Humans; Liver Neoplasms; Neoplasm Staging; Patient Safety; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 31872855
DOI: 10.1042/BSR20194019 -
BMJ Open Sep 2019This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis.
OBJECTIVES
This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018.
ELIGIBILITY CRITERIA
Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model.
RESULTS
This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), -1.02(95% CI -1.90 to -0.15)), CsA (SMD, -0.70 (95% CI -1.33 to -0.08)),CTX (SMD, -1.01 (95% CI -1.44 to -0.58)), MMF (SMD, -0.98 (95% CI -1.64 to -0.32)), MZB (SMD, -0.97 (95% CI -1.90 to-0.04]), TAC (SMD, -1.16 (95% CI -1.72 to -0.60)) and TAC+TW(SMD, -2.03 (95% CI -2.94 to -1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies.
CONCLUSIONS
This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN.
PROSPERO REGISTRATION NUMBER
CRD42018094228.
Topics: Adult; Cyclophosphamide; Drug Therapy, Combination; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Nephrotic Syndrome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Tacrolimus; Tripterygium
PubMed: 31511292
DOI: 10.1136/bmjopen-2019-030919 -
Cancer Biology & Therapy Jul 2020Up to now, no proven effective medical therapy for surgery and radiation-refractory anaplastic meningioma (AM) exists. Patients with vascular endothelial growth factor...
UNLABELLED
Up to now, no proven effective medical therapy for surgery and radiation-refractory anaplastic meningioma (AM) exists. Patients with vascular endothelial growth factor receptor 2 (VEGFR-2) positive meningiomas showed significantly shorter progression-free survival. Apatinib is a small-molecule antiangiogenic agent that selectively inhibits VEGFR-2. We report three cases of recurrent AM (VEGFR-2 positive) treated with apatinib. After apatinib treatment, the best outcome for all three patients was the partial response. The Progression-free survival was 17.3 months, 10.3 months, and 14+ months, respectively. The third patient lost follow-up after the last review. The overall survival was 28.5 months and 18 months, respectively. The main adverse events were hypertension, hand-foot syndrome, and myelosuppression. Apatinib is active in recurrent AM patients and this is the first report in the world. It is promising to launch a Phase II clinical trial of apatinib to further evaluate its efficacy on AM.
BACKGROUND
Anaplastic meningioma (AM) are rare and aggressive tumors with high recurrence rates despite optimal surgical or medical management. Up to now, no proven effective medical therapy, surgery, or radiation-refractory for AM exist. The progression-free survival (PFS) of patients with vascular endothelial growth factor receptor 2 (VEGFR-2)-positive meningiomas was significantly low. Apatinib (YN968D1) is a small-molecule antiangiogenic agent that selectively inhibits VEGFR-2.
CASE #1
A 47-year-old Asian female patient with malignant meningioma underwent four operations and three radiotherapies. She was given a 500 mg apatinib daily oral treatment, and the dosage was halved to 250 mg 3 months into the treatment. According to the Response Assessment in Neuro-Oncology (RANO) evaluation criteria, the best outcome during treatment was the partial response (PR) 6 months after the treatment. The PFS was 17.3 months, whereas the overall survival (OS) was 28.5 months. The best change in the Karnofsky performance scale (KPS) was a 10-point increase. The main adverse events included anemia (grade II), thrombocytopenia (grade II), and proteinuria (grade I).
CASE #2
A 71-year-old Asian woman with AM underwent two operations and two gamma knife stereotactic radiotherapies. She was given a 500 mg apatinib daily oral treatment with a follow-up period of 18 months. apatinib was taken orally for 10 months. According to the RANO evaluation criteria, the best outcome during treatment was PR. The PFS was 10.3 months, whereas the OS was 18 months. The best change in KPS was a 20-point increase. The main adverse events included hypertension (grade II), hand-foot syndrome (grade II), and fecal ocular blood (grade II). Case #3: A 16-year-old Asian girl with AM underwent two operations and two radiotherapies. She was given a 250 mg apatinib daily oral treatment with a follow-up period of 16 months. Apatinib was taken orally for 8 months. The patient did not follow-up after the last review of the brain-enhanced magnetic resonance imaging. According to the RANO evaluation criteria, the best outcome during treatment was PR. The PFS was 14+ months, and the best change in KPS was a 10-point increase. The main adverse events included hypertension (grade I) and hand-foot syndrome (grade I).
CONCLUSION
Apatinib is actively used in treating patients with recurrent AM. A randomized trial and phase II clinical trial of this inhibitor should be performed to further evaluate its efficacy in treating malignant meningioma.
Topics: Adolescent; Aged; Antineoplastic Agents; Female; Humans; Meningioma; Middle Aged; Pyridines; Retrospective Studies
PubMed: 32212907
DOI: 10.1080/15384047.2020.1740053 -
Expert Review of Hematology May 2020: Authors assessed the impact of ruxolitinib (RUX) on steroid-refractory graft-versus-host disease (SR-GVHD) patients.: Studies published before January 2019 were... (Meta-Analysis)
Meta-Analysis
: Authors assessed the impact of ruxolitinib (RUX) on steroid-refractory graft-versus-host disease (SR-GVHD) patients.: Studies published before January 2019 were identified by electronic search of MEDLINE, EMBASE, Cochrane Library, Clinical Trials.Gov and Web of Science databases.: Sixteen cohort studies (414 adults) were included whose methodological quality ranged from poor to good. Pooled outcomes such as the response rates, steroid dose reduction, 1-year overall survival, overall infection, and grade 3 to 4 cytopenia were calculated separately for adults with steroid-refractory acute GVHD (aGVHD) and chronic GVHD (cGVHD). Further, the overall response rates were analyzed according to the affected organ. Adults with aGVHD as well as cGVHD showed high response with RUX, and steroid dose reduction was observed in both cases. Infection rates and cytopenia were important safety concerns for both aGVHD and cGVHD.: Notwithstanding the need of randomized controlled trials to confirm the effect of RUX on SR-GVHD, response rates among adults with aGVHD and cGVHD seem to be high with the use of RUX as a salvage treatment, particularly in cases with gastrointestinal and cutaneous involvement. However, high rates of myelosuppression and infection remain a cause for concern regardless of aGVHD or cGVHD.
Topics: Adult; Allografts; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Nitriles; Pyrazoles; Pyrimidines; Survival Rate
PubMed: 32178541
DOI: 10.1080/17474086.2020.1738214 -
Journal of Gastroenterology and... Aug 2020The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor. This study aimed to evaluate hepatic arterial infusion... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND AIM
The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor. This study aimed to evaluate hepatic arterial infusion chemotherapy (HAIC) versus sorafenib (SORF) in the treatment of HCC with PVTT.
METHODS
Studies were identified online in Embase and MEDLINE before October 31, 2019. The end-points were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety.
RESULTS
Six studies with 417 cases were included in this systematic review. Meta-analyses demonstrated that HAIC is superior to SORF with respect to OS (hazard ratio [HR]: 0.50, 95% confidence interval: 0.38-0.66, P < 0.001) and PFS (HR: 0.47, 95% confidence interval: 0.31-0.73, P = 0.001) irrespective of research territoriality and study quality. Our systematic review also demonstrated that HAIC is superior to SORF with respect to DCR. Subgroup analysis demonstrated that the advantage is more obvious in the treatment of types III-IV PVTT with respect to OS (HR: 0.29, P < 0.001) and PFS(HR: 0.39, P < 0.001). HAIC caused more grades 3-4 neutropenia (HR: 10.71), anemia (HR: 7.55), leukopenia (HR: 10.38), and thrombocytopenia (HR: 13.09) than SORF. However, HAIC caused fewer cases of grades 3-4 aspartate aminotransferase rising (HR: 0.21), diarrhea (HR: 0.14), and hand-foot syndrome (HR: 0.14) than SORF.
CONCLUSIONS
This systematic review demonstrated that HAIC is superior to SORF in HCC with PVTT with respect to OS, PFS, and DCR, especially in HCC with types III-IV PVTT. HAIC caused more myelosuppression, whereas SORF is associated with diarrhea and hand-foot syndrome. Further randomized controlled trials are warranted.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Neoplasm Staging; Neoplastic Cells, Circulating; Portal Vein; Prognosis; Safety; Sorafenib; Survival Rate; Treatment Outcome; Venous Thrombosis
PubMed: 32052876
DOI: 10.1111/jgh.15010 -
International Journal of Clinical... Apr 2024Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.
BACKGROUND
Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer.
METHODS
We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain.
RESULTS
A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability.
CONCLUSION
Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.
Topics: Humans; Lung Neoplasms; Granulocyte Colony-Stimulating Factor; Carcinoma, Non-Small-Cell Lung; Docetaxel; Quality of Life; Small Cell Lung Carcinoma; Ramucirumab; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38353907
DOI: 10.1007/s10147-024-02469-4 -
Frontiers in Oncology 2020Chemotherapy usually induces a variety of side-effects in cancer treatment as it cannot tell normal cells apart from cancer cells and kills both. Chinese herbal medicine...
BACKGROUND
Chemotherapy usually induces a variety of side-effects in cancer treatment as it cannot tell normal cells apart from cancer cells and kills both. Chinese herbal medicine (CHM) has been regarded as a potential effective intervention for relieving the side-effects of chemotherapy in breast cancer patients.
OBJECTIVE
This study aims to conduct a comprehensive systematic review and meta-analysis to evaluate the efficacy of CHM as adjuvant therapy for reducing the chemotherapy-induced side-effects in the treatment of breast cancer.
METHODS
Main electronic databases were searched up to May 2020 for Randomized Controlled Trials (RCTs) evaluating the effect of CHM on breast cancer patients with chemotherapy. The PRISMA statement was adopted in this study and meta-analyses were performed.
RESULTS
The included studies showed unsatisfied quality. Results based on available literature indicated that the adjunctive use of CHM with chemotherapy may reduce the chemotherapeutic agents-associated adverse events, including nausea and vomiting, diarrhea, alopecia, myelosuppression, and impaired immune function.
CONCLUSION
A confident conclusion could not be have due to the lack of large scale and high quality trials.
PubMed: 33363030
DOI: 10.3389/fonc.2020.599073 -
BMC Health Services Research Dec 2022Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is...
BACKGROUND
Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim's value for money remains unclear.
OBJECTIVE
To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.
METHODS
A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020.
RESULTS
We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17-97.4%) and mortality rates (5.8-8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit.
CONCLUSIONS
Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.
Topics: Humans; Filgrastim; Granulocyte Colony-Stimulating Factor; Cost-Benefit Analysis; Chemotherapy-Induced Febrile Neutropenia; Polyethylene Glycols; Antineoplastic Agents; Lymphoma; Recombinant Proteins; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36585648
DOI: 10.1186/s12913-022-08933-z -
The Cochrane Database of Systematic... Mar 2021Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours.
OBJECTIVES
To assess the clinical effectiveness of single-agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcomes were overall survival and progression-free survival. Secondary outcomes included response rate, symptom palliation, toxicity, and health-related quality of life.
SEARCH METHODS
We conducted electronic searches of the Cochrane Register of Controlled Trials (CENTRAL) (2020, Issue 7), MEDLINE (1946 to 27th July 2020), Embase (1980 to 27th July 2020), and ISI Web of Science (1899 to 27th July 2020). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (July 2020); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles.
SELECTION CRITERIA
Parallel-group randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis.
MAIN RESULTS
Twenty-two trials met the inclusion criteria. Ten of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 3023, of whom approximately 2563 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was used in eight trials, gefitinib in nine trials, afatinib in two trials, cetuximab in two trials, and icotinib in one trial. The findings of FASTACT 2 suggested a clinical benefit for OS for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, as did the Han 2017 trial for gefitinib plus cytotoxic chemotherapy, but both results were based on a small number of participants (n = 97 and 122, respectively). For progression-free survival (PFS), a pooled analysis of four trials showed evidence of clinical benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.31; 95% confidence interval (CI) 0.25 to 0.39 ; 583 participants ; high-certainty evidence). A pooled analysis of two trials of gefitinib versus paclitaxel plus carboplatin showed evidence of clinical benefit for PFS for gefitinib (HR 0.39; 95% CI 0.32 to 0.48 ; 491 participants high-certainty evidence), and a pooled analysis of two trials of gefitinib versus pemetrexed plus carboplatin with pemetrexed maintenance also showed evidence of clinical benefit for PFS for gefitinib (HR 0.59; 95% CI 0.46 to 0.74, 371 participants ; moderate-certainty evidence). Afatinib showed evidence of clinical benefit for PFS when compared with chemotherapy in a pooled analysis of two trials (HR 0.42; 95% CI 0.34 to 0.53, 709 participants high-certainty evidence). All but one small trial showed a corresponding improvement in response rate with tyrosine-kinase inhibitor (TKI) compared to chemotherapy. Commonly reported grade 3/4 adverse events associated with afatinib, erlotinib, gefitinib and icotinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms; fatigue and anorexia were also associated with some chemotherapies. Seven trials reported on health-related quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, two trials showed improvement in one or more indices for the TKI compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy.
AUTHORS' CONCLUSIONS
Erlotinib, gefitinib, afatinib and icotinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged PFS compared to cytotoxic chemotherapy. We found a beneficial effect of the TKI compared to cytotoxic chemotherapy in adverse effect and health-related quality of life. We found limited evidence for increased OS for the TKI when compared with standard chemotherapy, but the majority of the included trials allowed participants to switch treatments on disease progression, which will have a confounding effect on any OS analysis. Single agent-TKI remains the standard of care and the benefit of combining a TKI and chemotherapy remains uncertain as the evidence is based on small patient numbers. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, afatinib or icotinib and is associated with greater toxicity. There are no data supporting the use of monoclonal antibody therapy. Icotinib is not available outside China.
Topics: Afatinib; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bias; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cetuximab; Crown Ethers; ErbB Receptors; Erlotinib Hydrochloride; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Paclitaxel; Pemetrexed; Progression-Free Survival; Protein Kinase Inhibitors; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 33734432
DOI: 10.1002/14651858.CD010383.pub3 -
European Journal of Haematology Dec 2019To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival... (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta-analysis.
METHODS
We searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma.
RESULTS
Six daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (≥CR) rate of 24%, very good partial response or better (≥VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P < .001. The HR for overall survival (OS) was 0.73 [0.52, 1.04], P = .09. In the network meta-analysis for patients ineligible for autologous stem-cell transplantation (ASCT), DRd regimen produced significant PFS advantage vs other first-line treatments (VMP HR:0.39 P < .001, Rd HR:0.55 P < .001, MPT HR:0.38 P < .001, and MP HR:0.22 P < .001); DVMP regimen also produced significant PFS advantage vs VMP (HR:0.50 P < .001), MPT (HR:0.49 P < .001), and MP (HR:0.28 P < .001). Among these first-line regimens (DRd, DVMP, VMP, Rd, MPT, and MP), DRd regimen had the highest probability to be the best intervention, with 83.4% and 91.0% probability to reach the longest PFS and OS, respectively. Toxicity consisted primarily of myelosuppression. And, the vital non-hematologic adverse events (AEs) were peripheral sensory neuropathy (41% of all grades) and upper respiratory tract infection (39% of all grades).
CONCLUSIONS
Daratumumab added to standard of care could produce clinical benefits in newly diagnosed patients with multiple myeloma. DRd and DVMP could be good combination options for those patients ineligible for ASCT.
Topics: Antibodies, Monoclonal; Autografts; Clinical Trials as Topic; Disease-Free Survival; Humans; Multiple Myeloma; Stem Cell Transplantation; Survival Rate
PubMed: 31444819
DOI: 10.1111/ejh.13317