Efficacy and safety of first-line combination therapy versus monotherapy for vitreoretinal lymphoma: a systematic review and meta-analysis
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ABSTRACT:
SUBMITTER: Gao J
PROVIDER: S-EPMC10664658 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.
| S-EPMC11301282 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is one of the cancers with the highest morbidity and mortality. Sorafenib used to be the main treatment for unresectable HCC patients. However, regimens based on immune checkpoint inhibitors (ICIs) have attracted attention in recent years because of their reported benefits. This study aimed to evaluate the efficacy and safety of monotherapy and combination therapy of ICIs as first-line treatment for unresectable HCC patients by conducting a systematic review, meta-analysis, and network meta-analysis.MethodsStudies published up to 11st August 2022 were searched from 4 commonly used databases, including PubMed, Web of Science, Embase, and Clinical trials.gov. All eligible clinical trials were included. Data about reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were extracted.ResultsOf the 8579 studies retrieved, 24 met the inclusion criteria. In patients with unresectable HCC taking ICIs-based therapy as first-line treatment, the pooled result of median PFS and median OS was 5.76 months (95% CI 4.82-6.69) and 16.35 months (95% CI 15.19-17.51) The ORR and DCR were 25.1% (95% CI 20.8-29.5%) and 75.2% (95% CI 70.3-80.2%) measured by RECIST v1.1 or 40.2% (95% CI 31.7-48.6%) with 75.2% (95% CI 68.3-82.1%) measured by mRECIST v1.1. Compared to sorafenib, ICIs-based therapy significantly prolonged OS. The combination treatment of sintilimab plus IBI305 had the highest ORR, while atezolizumab plus bevacizumab had the highest DCR. The pooled incidence of any grade TRAEs was 82.3% (95% CI 73.9-90.7%), with highest incidence appeared in dysphonia.ConclusionsThis study demonstrated that first-line ICIs-based therapies could provide survival benefits for patients with unresectable HCC, with manageable TRAEs. The potential of combination treatment to become the new treatment trend in clinical practice is promising.
| S-EPMC9519826 | biostudies-literature
Project description:BackgroundClostridium difficile infection (CDI) has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.MethodsA comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated and reported.ResultsOf the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients) were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00), p = 0.05) or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96), p = 0.83); however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80), p = 0.006). No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45), p = 0.98) or severe CDI (OR = 0.98, 95% CI (0.63, 1.53), p = 0.94) or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26), p = 0.56). In addition, there was no significant difference in the rate of adverse events (AEs) between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74), p = 0.41). In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51), p < 0.0001).ConclusionsMetronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI. Combination therapy is not superior to monotherapy because it appears to be associated with an increase in the rate of AEs.
| S-EPMC4621873 | biostudies-literature
Project description:BackgroundEndocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis.MethodsWe performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events.ResultsWe identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg.ConclusionsFulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.
| S-EPMC5571723 | biostudies-literature
Project description:BackgroundSoil-transmitted helminthiasis remains a daunting challenge to global health, exerting its greatest toll on resource-limited regions of the world. A dual drug approach using the co-administration of ivermectin and albendazole has shown promising results in comparison to the traditional monotherapy strategy. In light of this, a systematic review and meta-analysis of randomized controlled trials was conducted.MethodsSeveral electronic databases including PubMed, Cochrane Central, Google Scholar, and Embase were explored to search for relevant studies from inception to September 2023. The Cochrane Risk of Bias Tool for Randomized Controlled Studies was utilized to evaluate the quality of studies.ResultsA total of 8 randomized controlled trials, reporting 10 patient populations, were included. The treatment of trichuriasis significantly favored the dual therapy regimen of ivermectin-albendazole over albendazole-only monotherapy (risk ratio [RR]: 2.86; 95% confidence interval [CI]: 1.66-4.93; P = .0002), with no significant differences observed for ascariasis and hookworm. The treatment of trichuriasis and hookworm significantly favored the dual therapy regimen of ivermectin-albendazole over ivermectin-only monotherapy (RR: 1.86; 95% CI: 1.56-2.21; P < .00001 and RR: 2.31; 95% CI: 1.23-4.31; P = .009, respectively). There were no statistically significant differences between dual therapy and monotherapy in terms of adverse effects.ConclusionThese findings highlight the nuanced effectiveness of combined therapy specific to certain helminth types, in addition to their comparable safety profiles, thereby providing pivotal insights that contribute to the evolving landscape of soil-transmitted helminth treatment strategies.
| S-EPMC11749739 | biostudies-literature
Project description:BackgroundTargeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance.MethodsPubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool.ResultsNine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs.ConclusionsLorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.
| S-EPMC8606689 | biostudies-literature
Project description:The effectiveness and safety of combination treatments such as chemoimmunotherapies in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) remain controversial. Bruton tyrosine kinase inhibitors (BTKis) are an effective therapy for CLL/SLL patients. This meta-analysis aimed to compare the efficacy and safety of BTKis versus combination therapy in CLL/SLL patients. We searched the PubMed, Cochrane, Medline, and Embase databases through February 2023 for relevant randomized controlled trials (RCTs). Four RCTs (including 1510 patients) were found and met the inclusion criteria. Progression-free survival (PFS) was significantly improved with BTKis when compared to the combination therapy (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.22-0.40), while a pooled analysis of overall survival did not favor single-agent BTKis over the combination therapy (HR, 0.87; 95% CI, 0.67-1.15). We observed consistent benefits for PFS among patients with high-risk disease characteristics. Although there was no difference in complete response between the two arms (risk ratio (RR), 0.54; 95% CI, 0.20-1.46), BTKi use was related to a better overall response rate (RR, 1.10; 95% CI, 1.04-1.16). The risk of grade ≥3 adverse events (AEs) was comparable between the two arms (RR, 0.82; 95% CI, 0.55-1.23). However, the risk of grade ≥3 AEs was significantly lower in the second-generation BTKi group than in the combination therapy group (RR, 0.73; 95% CI, 0.54-0.98). Overall, BTKis have superior efficacy compared to the combination regimens in patients with untreated or treated CLL/SLL without excess toxicity. Further studies are needed to confirm these results and determine the optimal therapy for managing patients with CLL/SLL.
| S-EPMC10093473 | biostudies-literature
Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease group. Ibrutinib's monotherapy or combination therapy is effective in relapsed/refractory (R/R) DLBCL. However, the treatment response in R/R DLBCL varies from 15% to 90% with different regimens, and the tolerance remains controversial.Areas of uncertaintyThe efficacy and safety of ibrutinib monotherapy or combination therapy in patients with R/R DLBCL remain uncertain.Data sourcesThe PubMed, CBM, MEDLINE, Cochrane Library, and Embase databases were searched from their inception to July 2021.Therapeutic advancesThe total complete remission rate (CRR) and overall response rate in R/R DLBCL patients treated with ibrutinib were 26% and 49%, respectively. The CRR of ibrutinib combination therapy was significantly higher than the ibrutinib monotherapy (45% vs. 19%). Moreover, the CRR of patients was 40% in double expressing lymphoma, 35% in central nervous system lymphoma, and 33% in nongerminal center B-cell-like (non-GCB) DLBCL, which was higher than the 8% in those with the GCB subtype. The pooled median PFS and overall survival were 5.57 and 10.17 months, respectively. GCB-DLBCL had the worst overall survival (5.1 months). Nevertheless, we found that combination regimens had no survival advantage compared with monotherapy (P > 0.05), indicating that combination therapy was only a transitional treatment and bridge for chimeric antigen receptor T cells or other treatments. Moreover, 12% of patients on ibrutinib combination therapy had ≥grade 3 adverse events compared with 9% on ibrutinib monotherapy.ConclusionsIbrutinib monotherapy or combination therapy was safe and effective in treating R/R DLBCL with tolerable adverse reactions.
| S-EPMC11698132 | biostudies-literature
Project description:IntroductionSeveral maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients.MethodsMEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes.ResultsWe included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months.ConclusionThis study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.
| S-EPMC8674688 | biostudies-literature
Project description:ABSTRACT Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 mg/formoterol fumarate 12 mg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 mg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV1/FVC <0.70, using ICS, LAMA, or LABA for ≥1 month were included. Subjects were randomized (1:1) to GB/FF or GLY for 12 weeks. The primary efficacy endpoint was the change from baseline in peak FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI/2017/02/007814). Results: Between March 2017 and July 2018, 331 patients were enrolled and randomized into GB/FF FDC (165 patients) and GLY monotherapy (166 patients) groups. At week 12, the difference in change from baseline in the peak FEV1 for GB/FF DPI versus GLY was 0.115 L (SE = 0.02; 95% CI = 0.061, 0.170; P < 0.0001). Trough FEV1 increased significantly in the GB/FF group compared to the GLY group with a treatment difference of 0.078 L (SE = 0.02; 95% CI = 0.015, 0.14; P = 0.01). There were no significant differences in adverse events between the groups. Conclusion: FDC of GB/FF (12.5/12 mg twice daily) as a DPI provides superior bronchodilation and lung function improvement over GLY (50 mg once daily) monotherapy. It is safe and well tolerated in symptomatic COPD patients.
| S-EPMC9746267 | biostudies-literature