scholarly journals Front-Line Therapy in EGFR Exon 19 Deletion and 21 Leu858Arg Mutations in Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Tongji Xie ◽  
Zihua Zou ◽  
Chengcheng Liu ◽  
Yixiang Zhu ◽  
Ziyi Xu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Cochrane Library ◽  
First Line ◽  
Exon 19 Deletion ◽  
Cumulative Probabilities

Objective. This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations). Methods. We conducted a systematic review and network meta-analysis (NMA) by searching and analyzing RCTs on PubMed, Embase, Cochrane Library, ASCO.org, and ESMO.org, from inception to September 30th, 2020. Results. Nineteen RCTs involving 5450 patients were finally included in this study, covering 10 different treatment strategies. The Bayesian ranking results suggested that, in terms of PFS, in the overall population and in patients with 19del mutation, osimertinib was most likely to rank the first, with the cumulative probabilities of 41.89% and 45.73%, respectively, while for patients with 21 Leu858Arg mutation, standard of care (SoC, represents first-generation EGFR-TKIs in this NMA) + chemotherapy was most likely to rank the first, with the cumulative probabilities of 30.81% in PFS. Moreover, SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively. In contrast, for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%. Conclusions. In this NMA, osimertinib and SoC combined with chemotherapy would be the optimal first-line treatment options for advanced NSCLC patients harboring EGFR 19 deletion mutation and 21 Leu858Arg mutation, respectively. This finding is likely to be adopted in clinical practice and provide guidance for future clinical study design. Systematic review registration: INPLASY2020100059.

scholarly journals Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis

BMJ ◽  
2019 ◽  
pp. l5460 ◽  
Author(s):  
Yi Zhao ◽  
Jingting Liu ◽  
Xiuyu Cai ◽  
Zhenkui Pan ◽  
Jun Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Combination Treatments ◽  
Exon 19 Deletion ◽  
Egfr Mutated

AbstractObjectiveTo compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).DesignSystematic review and network meta-analysis.Data sourcesPubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.Eligibility criteria for selecting studiesPublished and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.Results18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.ConclusionsThese results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.Systematic review registrationPROSPERO CRD42018111954.

Rituximab Maintenance (MR) for Patients with Mantle Cell Lymphoma (MCL) – a Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4466-4466 ◽  
Author(s):  
Liat Vidal ◽  
Anat Gafter-Gvili ◽  
Martin Dreyling ◽  
Michele Ghielmini ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Infection Rate ◽  
Induction Therapy ◽  
Research Funding ◽  
Meta Analysis ◽  
Small Sample ◽  
Interferon Alfa ◽  
Cochrane Library ◽  
First Line

Abstract Background MCL is characterized by a dismal long term prognosis with a median overall survival of 3-5 years. The addition of rituximab to induction chemotherapy improved significantly response rates of patients with MCL. MR treatment for these patients has the potential to further improve disease control and overall survival (OS). The few trials that addressed that question showed inconsistent results. Aims We performed a systematic review and meta-analysis of RCTs in order to assess the effect of MR on clinical outcomes of patients with MCL. Methods We included RCTs that compared MR to no treatment or other treatment for patients with MCL, either in first line or relapsed disease. In March 2014 we searched The Cochrane Library, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the quality of the trials and extracted data. The primary outcome was all cause mortality. Secondary outcomes included progression free survival (PFS) and infectious adverse events. Relative risk (RR) for dichotomous data and hazard ratio (HR) for time to event datawere estimated and pooled using random-effects model. Results We identified 3 trials, conducted between the years 1998 to 2010 and randomizing 434 adult patients with MCL. Most patients were males, with a median age ranging from 61 to 70 years, and predominantly good performance status. Seventy-nine percent of the patients received their first line of treatment. MIPI score was reported in one trial. Induction therapy included rituximab in all three trials. In two trials additional chemotherapy induction was applied consisting of fludarabine, cyclophosphamide (FC) and mitoxantrone in one trial (Forstpointner, Blood 2006), and cyclophosphamide, vincristine, adriamycin, prednisone (CHOP) or FC in the other (Kluin-Nelemans, NEJM 2012); in the third trial rituximab was given alone (Ghielmini, JCO 2005). The control group received no maintenance in two trials and interferon alfa in one trial. All included trials are judged at low risk of selection bias, none were blinded. Mortality rate decreased with MR compared to no MR or interferon alfa RR 0.67, 95% CI 0.46 to 0.98, I2 of heterogeneity 54%, 392 patients (Figure). PFS improved with MR compared to no MR or interferon alfa: HR 0.60, 95% CI 0.44 to 0.82, I2 of heterogeneity = 0. There was no statistically significant difference in infection rate with or without MR (RR 0.80, 95% CI 0.37 to 1.69, 419 patients). Conclusions The results of this meta-analysis support a survival benefit of MR in patients with first line or relapsed/refractory MCL who responded to induction therapy. Additionally, there is a significant improvement of PFS benefit of MR. The absence of significant increase of infection rate as opposed to MR in follicular lymphoma may be attributed to the small sample size. Based on these results patients treated for both first line and relapsed/refractory MCL should receive MR after achieving response to induction. Figure: Pooled RR of mortality of patients with MCL who responded to induction and treated with MR compared to observation or interferon alfa. Figure:. Pooled RR of mortality of patients with MCL who responded to induction and treated with MR compared to observation or interferon alfa. Disclosures Vidal: Roche: unrestricted grant Other. Ghielmini:Roche: Research Funding, Speakers Bureau. Unterhalt:Roche: Travel Support Other. Shpilberg:Roche: Consultancy, Research Funding.

Management of recurrent pancreatic cancer after surgical resection: Systematic review, evidence mapping, and meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 448-448
Author(s):  
Jong-Chan Lee ◽  
Jin-Hyeok Hwang ◽  
Jaihwan Kim ◽  
Hyoung Woo Kim ◽  
Jongchan Lee
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Treatment Option ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Treatment Options ◽  
Cochrane Library ◽  
Metastatic Recurrence ◽  
Evidence Mapping

448 Background: Although almost patients with surgically resected pancreatic cancer (PC) experience recurrence, the optimal treatment option of recurrent PC is still unclear. Numerous studies have been reported about this issue, but all the scattered evidences are too small and heterogeneous to reach a conclusion. The aim of this systematic review is to perform ‘evidence mapping’ and subgroup meta-analysis. Methods: In regards to local recurrence and metastatic recurrence respectively, four treatment options including re-operation (ReOP), chemotherapy (CTx), radiotherapy (RT), best supportive care (BSC) were searched from Medline, Embase, Cochrane library, Scopus and Web of Science from 1976 to April 30, 2016. To visualize the mapping of evidence, we established a web-based mapping tool ( http://plotting-e-map.com ) and used it. In the treatment options with selected study types, subgroup meta-analyses were conducted using overall survival as a primary endpoint. Results: Among detected 12,040 studies, a total of 162 studies were included. In locally recurrent PC, overall 126 studies (39 of ReOP, 40 of CTx, 37 of RT, and 10 of BSC) were included. Median overall survival (OS) of each treatment option was 16.1 months (95% CI 4.9–22.1, I2 52%) for ReOP, 14.9 month (95% CI 7.5–18.9, I2 63%) for CTx, 13.8 months (95% CI 5.6–17.0, I2 59%) for RT. In metastatic recurred PC, overall 36 studies (10 of ReOP, 22 of CTx, no RT, 4 of BSC) were included. Median OS’s were 8.3 months (95% CI 3.6–11.2, I2 56%) for Re-OP, and 6.8 months (95% CI 4.1–9.5, I2 33%) for CTx. Conclusions: During recent 40 years, evidences showed that re-operation for highly selected patients with locally and metastatic recurrent PC could be a considerable therapeutic option. However, since the heterogeneity among the studies is relatively high, more prospective and comparative studies about re-operation with multimodality treatment are needed.

Prevalence and Risk Factors of Relapse in Patients with ANCA-Associated Vasculitis Receiving Cyclophosphamide Induction: A Systematic Review and Meta-analysis of Large Observational Studies

Rheumatology ◽  
2020 ◽  
Author(s):  
Peng He ◽  
Jin-ping Hu ◽  
Xiu-juan Tian ◽  
Li-jie He ◽  
Shi-ren Sun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Baseline Serum ◽  
Anca Associated Vasculitis ◽  
Hazard Ratios ◽  
Post Hoc ◽  
Cumulative Probabilities ◽  
Relapse Rates

Abstract Background Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse. Methods We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed. Results Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10–0.14), 0.33 (0.29–0.38), and 0.47 (0.42–0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine). Conclusions Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.

scholarly journals Remotely delivered interventions to support women with symptoms of anxiety in pregnancy: a mixed methods systematic review of quantitative and qualitative evidence (Preprint)

2021 ◽  
Author(s):  
Kerry Evans ◽  
Stefan Rennick-Egglestone ◽  
Serena Cox ◽  
Yvonne Kuipers ◽  
Helen Spiby
Keyword(s):  
Systematic Review ◽  
Pregnant Women ◽  
Quantitative Data ◽  
Meta Analysis ◽  
Treatment Options ◽  
Social Science Citation Index ◽  
Cochrane Library ◽  
Access To Treatment ◽  
On Line ◽  
In Pregnancy

BACKGROUND Symptoms of anxiety are common in pregnancy, with severe symptoms associated with negative outcomes for women and babies. Low level psychological therapy is recommended as first line treatment options for women with mild to moderate anxiety, with the aim to prevent an escalation of symptoms and provide women with coping strategies. Remotely delivered interventions have been suggested to improve access to treatment and support for women in pregnancy and provide a cost-effective, flexible and timely solution. OBJECTIVE To identify and evaluate remotely delivered, digital or on-line interventions to support women with symptoms of anxiety in pregnancy. METHODS A mixed method systematic review following a convergent segregated approach to synthesise the qualitative and quantitative data. The ACM Digital Library, AMED, ASSIA, CRD, CENTRAL, the Cochrane Library, CINAHL, EMBASE, HTA, IEEE Xplore, JBI, Maternity and Infant Care, Medline, PsycINFO and the Social Science Citation Index were searched in October 2020. Quantitative or qualitative primary research including pregnant women which evaluated remotely delivered interventions reporting measures of anxiety, fear, stress, distress, women’s views, feedback and opinions were included in the review. RESULTS Three qualitative and 14 were quantitative studies included. Populations included a general antenatal population, and pregnant women with anxiety and depression, fear of childbirth, insomnia and pre-term labour. Interventions included CBT, Problem Solving, Mindfulness and Educational designs. Most interventions were delivered via on-line platforms and 8 included direct contact from trained therapists or coaches. A meta-analysis of the quantitative data found for I-CBT and facilitated interventions there was observed beneficial effect in relation to the reduction of anxiety scores (SMD=-0.49; 95% CI=-0.75 to -0.22; SMD=-0.48; 95% CI=-0.75 to -0.22). However, due to limitations in the amount of available data and study quality, the findings should be interpreted with caution. Synthesised findings from quantitative and qualitative data found some evidence to suggest that interventions are more effective when women are motivated to maintain regular participation in interventions. Participation may be enhanced by providing regular contact with therapists, targeting interventions for women with anxiety symptoms; providing peer support forums; including components of relaxation and cognitive based skills; and providing sufficient sessions to develop new skills without being too time consuming. CONCLUSIONS There is limited evidence to suggest that pregnant women may benefit from remotely delivered interventions. The synthesised findings highlighted components of interventions which may improve the effectiveness and acceptability of remotely delivered interventions. These include providing women with contact with a therapist, healthcare professional or peer community. Women may be more motivated to complete interventions which are perceived as relevant or tailored to their needs and situations. Remote interventions may also provide women with greater anonymity to help them feel more confident in disclosing their symptoms.

First Line Treatment of Advanced Stage Hodgkin Lymphoma with Six Cycles of BEACOPPescalated Results in Superior Overall Survival Compared to ABVD: Results of a Network Meta-Analysis Including 10,011 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 551-551
Author(s):  
Peter Borchmann ◽  
Sven Trelle ◽  
Michaela Rancea ◽  
Heinz Haverkamp ◽  
Volker Diehl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Initial Treatment ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 551 Background: The best treatment strategy for advanced stage Hodgkin lymphoma (HL) is still a matter of debate. The German Hodgkin Study Group (GHSG) advocates aggressive treatment with BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) to cure as many patients as possible with first-line therapy. However, BEACOPPescalated may expose patients to excessive toxicity. Treatment with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is supposed to be better tolerable. Proponents of primary ABVD therapy acknowledge a lower progression-free survival (PFS) compared to BEACOPPescalated. However, they argue that relapsing patients can subsequently be cured by high-dose chemotherapy resulting in comparable overall survival (OS). All trials evaluating these two strategies directly were either very small or included patient subgroups only. Although they congruently showed a significant PFS advantage for BEACOPPescalated, they were not powered to detect differences in OS, which obviously is the most important endpoint. Purpose: To assess the benefits and risks of different initial treatment strategies for adult patients with advanced stage HL and to provide patients and physicians with a high-level evidence for treatment decisions. Methods: Data Sources: We developed sensitive search strategies for CENTRAL, MEDLINE, and conference proceedings (searched from 01/1980 to 03/2012). Missing data was obtained from investigators. Study selection: Randomized trials that compared at least two out of twelve pre-defined chemotherapy regimens in adults with advanced stage HL. Two authors independently assessed studies for eligibility. Data extraction: We extracted data and assessed quality of trials in duplicate. The primary outcome was OS. Secondary outcomes included freedom-from-treatment failure (FFTF) and secondary malignancies. Data relates to four or five years of follow-up depending on the status of the trial. Data synthesis: We pooled data using network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian random-effects model. Results are reported relative to ABVD with a hazard ratio (HR) >1 indicating superiority of ABVD. Results: 1,984 references were identified, of which 77 publications, reporting 14 trials, evaluating 11 different regimens were included. A total of 10,011 patients with 59,000 patient-years of follow-up were evaluable for the analyses of survival outcomes. Six cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 were associated with the lowest risk for death of any cause (HR 0.38, 95%-CrI 0.20 to 0.75 and HR 0.43, 95%-CrI 0.22 to 0.86, respectively). Assuming a five-year survival rate of 89% for ABVD this would result in a 5-year survival benefit of 7% and 6% for 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14, respectively (95%-CrI 3% to 9% and 2% to 9%, respectively). Eight cycles of BEACOPPescalated were also statistically significantly better as compared to ABVD but the effect was less pronounced. All other treatment strategies showed no statistically significant difference to ABVD. Similar results were obtained for FFTF. Between-trial heterogeneity was negligible in both analyses (tau-square 0.01 and 0.05, respectively). Overall, 327 secondary malignancy and 109 leukemia events accumulated over 57,529 patient-years of follow-up. Given the low number of events we were not able to accurately quantify the risk associated with each regimen; however, Stanford V might be associated with the lowest risk and C(M)OPP/EBV/CAD with the highest risk for secondary leukemias. Limitations: Some of the regimens were only evaluated in one trial. The number of secondary malignancies, especially leukemias, was low. Conclusions: The comparison of different first-line treatment strategies for advanced stage HL in this network meta-analysis shows a significant and relevant OS benefit for both, 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 over standard ABVD treatment. This analysis provides the currently best available evidence on OS of different initial treatment strategies for advanced stage HL patients and therefore adds valid and important information for both, patients and physicians. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A systematic review and meta-analysis of nab-paclitaxel mono-chemotherapy for metastatic breast cancer

2020 ◽  
Author(s):  
Haili Lu ◽  
Siluo Zha ◽  
Wei Zhang ◽  
Qiang Wang ◽  
Daozhen Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
First Line ◽  
Line Therapy ◽  
Mixed Line

Abstract Background Various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC). The safety and efficacy of nab-paclitaxel needs to be systematically evaluated. Methods Electronic searches for prospective clinical trials containing nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analyzed from the included studies according to different purposes using systematic review and meta-analysis. Results 22 studies with 3287 MBC patients were included. 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. 1966 MBC patients (60.40%) received nab-paclitaxel weekly, while 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) biweekly. The overall incidence of all grades neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue was 52% (95% CI, 38%-66%), 58% (95% CI, 43%-73%), 58% (95% CI, 48%-68%), and 49% (95% CI, 41%-56%) respectively. The overall response rate (ORR) was 40% (95% CI, 35%-45%) and the clinical benefit rate (CBR) was 66% (95% CI, 59%-73%) following nab-paclitaxel monotherapy. The median progression free survival (PFS) was 7.64 months (95% CI, 6.89–8.40 months) and the median overall survival (OS) was 24.51 months (95% CI, 21.25–27.78 months). According to the meta-regression analysis, grade 3/4 neutropenia occurred less frequently in Her-2 negative patients compared with all population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed higher ORR (P = 0.006) and longer PFS (P = 0.045). Patients who received further-line therapy was demonstrated to have shorter median OS versus first- and mixed-line therapy. Efficacy outcomes were not affected by the administration schedule. However, patients appeared to have more superior ORR (P = 0.044) and longer PFS (P = 0.03) along with the increasing dosage of nab-paclitaxel under the same schedule. Conclusions Both weekly and triweekly nab-paclitaxel mono-chemotherapy were proved to be effective for MBC with generally reasonable toxicity profiles. Higher ORR, longer PFS and OS would be achieved in patients treated with nab-paclitaxel as first line. Increasing nab-paclitaxel dosage would result in better tumor control (higher ORR and PFS). Changing nab-paclitaxel schedule had no benefit on ameliorating the overall survival.

scholarly journals Decreased mortality and increased side effects in COVID-19 patients treated with IL-6 receptor antagonists: systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jishnu Malgie ◽  
Jan W. Schoones ◽  
Maurice P. Zeegers ◽  
Bart G. Pijls
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Mortality Risk ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Baseline Risk ◽  
Cochrane Library ◽  
Receptor Antagonists ◽  
Impaired Liver Function ◽  
Baseline Mortality

AbstractThere is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.

scholarly journals Addition of Induction or Consolidation Chemotherapy in Definitive Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Alone for Patients With Unresectable Esophageal Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianing Wang ◽  
Linlin Xiao ◽  
Shuai Wang ◽  
Qingsong Pang ◽  
Jun Wang
Keyword(s):  
Systematic Review ◽  
Esophageal Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Cochrane Library ◽  
Consolidation Chemotherapy ◽  
Metastasis Rate ◽  
Short Time

BackgroundConcurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal carcinoma patients who are not surgical candidates. The efficacy of induction chemotherapy (IC) or consolidation chemotherapy (CCT) for unresectable esophageal cancer (EC) treated with CCRT is unclear. We performed a systematic review and meta-analysis of published papers to evaluate the potential benefit of IC or CCT for patients with EC.MethodsEligible studies of IC followed by CCRT (IC-CCRT) vs. CCRT alone or CCRT followed by CCT (CCRT-CCT) vs. CCRT alone were retrieved through extensive searches of the PubMed, Science Direct, Embase, and Cochrane Library databases from the establishment of the database to July 31, 2021. Data such as 1-, 2-, 3-, and 5-year overall survival (OS), local recurrence rate (LRR), and distant metastasis rate (DMR) were collected for meta-analysis to evaluate the efficacy of IC/CCT.ResultsFour studies of IC-CCRT vs. CCRT including 836 EC patients and six studies of CCRT-CCT vs. CCRT including 1,339 patients with esophageal squamous cell carcinoma (ESCC) were finally identified in our analysis. Both IC-CCRT group [hazard ratio (HR) 0.446, 95% CI 0.286–0.693; p < 0.001] and CCRT-CCT group (HR 0.542, 95% CI 0.410–0.716; p < 0.001) exhibited statistically significant improvement in 1-year OS rate compared to that of CCRT, while the 2-year OS rate of IC-CCRT (HR 0.803, 95% CI 0.589–1.095; p = 0.166) or CCRT-CCT (HR 0.783, 95% CI 0.600–1.022; p = 0.072) was similar with that of CCRT. And the 3-year OS rate between IC-CCRT and CCRT was similar (HR 1.065, 95% CI 0.789–1.439; p = 0.680). However, comparing with CCRT alone, the CCRT-CCT group had lower DMR [odds ratio (OR) 1.562, 95% CI 1.090–2.240; p = 0.015] and higher 3-year OS rate (HR 0.786, 95% CI 0.625–0.987; p = 0.039). Besides, no differences were observed between the CCRT-CCT and CCRT groups in 5-year OS rate (HR 0.923, 95% CI 0.706–1.205; p = 0.555) and LRR (OR 0.899, 95% CI 0.686–1.179; p = 0.441).ConclusionThe study revealed the short-time survival benefit of additional IC or CCT compared to CCRT alone for patients with unresectable EC, and CCRT followed by CCT could significantly reduce the risk of distant metastases.

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