Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

e18336 Background: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Methods: Drugs approved for the treatment of solid tumors between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes or dysregulated pathways (group 1), anti-angiogenic drugs (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the reports of randomized trials supporting registration and pooled in a meta-analysis. Odds ratios (ORs) for rates of toxic death, treatment discontinuation and grade 3-4 toxicity were compared relative to control groups. The Micromedex Red Book was used to calculate the monthly price of each agent. Results: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a lesser degree with groups 3 and 4 than with groups 1 and 2, (pooled HR:0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference < 0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR:0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no statistically significant difference between groups. There was limited to no correlation between drug pricing and efficacy. Conclusions: Compared to control groups, chemotherapy improves efficacy to a lesser degree than the other groups. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.

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Physiotherapy and Pelvic Floor Muscle Exercises for the Prevention and Treatment of Pregnancy-Related Pelvic Floor Dysfunctions: A Systematic Review and Meta-analysis

International Journal of Women s Health and Reproduction Sciences ◽

10.15296/ijwhr.2020.20 ◽

2019 ◽

Vol 8 (2) ◽

pp. 125-132

Author(s):

Fahime Khorasani ◽

Fariba Ghaderi ◽

Parvin Sarbakhsh ◽

Parisa Ahadi ◽

Elahe Khorasani ◽

...

Keyword(s):

Systematic Review ◽

Pelvic Floor ◽

Pelvic Floor Muscle ◽

Meta Analysis ◽

Cochrane Library ◽

Control Groups ◽

Pelvic Floor Muscle Exercises ◽

Significant Difference ◽

Prevention And Treatment ◽

Pfm Strength

Objectives: The present systematic review focused on the prevention or treatment of three main types of pelvic floor dysfunctions (PFDs) specifically pelvic organ prolapse (POP), urinary incontinence (UI), and fecal incontinence (FI) using physiotherapy and pelvic floor muscle exercises (PFMEs). With regard to the breadth of the problem, there is not much evidence grounded on the best management. The main purpose of this systematic review was to evaluate the effects of physiotherapy and PFMEs on the prevention and treatment of pregnancy-related PFDs; namely, POP, FI, and UI. Therefore, this review incorporated studies comparing the use of physiotherapy and PFMEs with every other existing interventions. Methods: This systematic review and meta-analysis was conducted on randomized-controlled-trial (RCT) articles and quasi-RCT designs through a search in the studies published with no time limits until December 2017 in the databases of PubMed (Medline), Web of Science, Scopus, Embase, Cochrane Library, and ProQuest. The meta-analysis was also applied for data synthesis. Moreover, heterogeneity was assessed using Cochran’s Q test and I2 index. Results: A total number of 26 RCTs were examined in this review in which the outcome variables were related to POP, UI, and FI prevalence; POP, UI, and FI severity, as well as pelvic floor muscle (PFM) strength and endurance. In most articles, UI prevalence or severity in intervention groups had significantly improved compared with those in controls. The number of studies examining POP and FI was also relatively low. In two studies, FI severity or prevalence in intervention groups had significantly enhanced in comparison with those in control groups; however, FI prevalence in two articles had been reported lower in intervention groups than that in control groups although no significant difference had been observed. There was also no significant improvement in intervention groups in two other studies in this respect. Besides, three articles had not reported traces of improvement in POP, as well as a significant difference between intervention and control groups. Nevertheless, two studies had found a significant improvement in POP in this regard. Based on meta-analysis results for the variable of PFM strength, Cochran’s Q test (P<0.001) and I2 index (90.02) indicated heterogeneity between studies; so, a random-effect meta-analysis was applied to estimate overall effect sizes. The overall mean differences following intervention between the study groups were also equal to 6.94, with a 95% CI (1.36 to 12.52). Conclusions: It was concluded that physiotherapy and PFMEs might have effects on pregnancy-related UI, but they had not consistently reduced FI severity or prevalence and failed to constantly improve POP.

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Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Current Cancer Therapy Reviews ◽

10.2174/1573394717666210616152341 ◽

2021 ◽

Vol 17 ◽

Author(s):

Vinod Solipuram ◽

Harish Gopalakrishna ◽

Gayatri Naira ◽

Akhila Mohan

Keyword(s):

Pancreatic Cancer ◽

Placebo Group ◽

Febrile Neutropenia ◽

Adverse Events ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Thromboembolic Events ◽

Serious Adverse Events ◽

Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

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Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

Current Oncology ◽

10.3747/co.26.4203 ◽

2019 ◽

Vol 26 (1) ◽

Cited By ~ 1

Author(s):

Y. Yang ◽

R. Chen ◽

T. Sun ◽

L. Zhao ◽

F. Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Meta Analysis ◽

Progression Free Survival ◽

Efficacy And Safety ◽

First Line ◽

Combined Androgen Blockade ◽

Hazard Ratios ◽

Significant Difference ◽

Grade 3 ◽

Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

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Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis

Cancers ◽

10.3390/cancers12103026 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3026

Author(s):

Amos Stemmer ◽

Inbal Shafran ◽

Salomon M. Stemmer ◽

Daliah Tsoref

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Progression Free Survival ◽

Wild Type ◽

Brca Mutations ◽

Increased Risk ◽

Significant Difference ◽

Indirect Comparisons

Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.

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Effects of acupuncture on breast cancer-related lymphoedema: a systematic review and meta-analysis of randomised controlled trials

Acupuncture in Medicine ◽

10.1136/acupmed-2018-011668 ◽

2019 ◽

Vol 37 (1) ◽

pp. 16-24

Author(s):

Xinyan Zhang ◽

Xiuli Wang ◽

Bingyan Zhang ◽

Sa Yang ◽

Dongling Liu

Keyword(s):

Breast Cancer ◽

Elbow Joint ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Breast Cancer Treatment ◽

Control Groups ◽

Significant Difference ◽

Effectiveness Index ◽

Randomised Controlled ◽

And Control

Objective: Breast cancer-related lymphoedema (BCRL) is a common complication after breast cancer treatment. We investigated whether acupuncture could be used to manage limb oedema in women after breast cancer surgery. Methods: The Cochrane Library, PubMed, Embase, Web of Science, CINAHL, and four Chinese databases were electronically searched for papers published through November 2017. Randomised controlled trials (RCTs) of acupuncture for BCRL were included. Results: In total, six RCTs with 318 patients were identified. The main analysis revealed a positive overall effect of acupuncture intervention on pre/post-treatment differences in the diameter of the elbow joint, reductions in upper limb lymphoedema and effectiveness index based on arm measurement data in patients with breast cancer. Two studies evaluating the outcome of acupuncture on the diameter of the elbow joint found a significant reduction in diameter between the acupuncture and control groups (weighted mean difference (WMD) 6 cm, 95% CI 5.11 to 6.89 cm; P<0.001). The same two studies investigated the effect of acupuncture on upper limb lymphoedema reduction and found a significant difference between the acupuncture and control groups (risk ratio 1.4, 95% CI 1.17 to 1.67; P<0.001). Two other studies used the effectiveness index to assess the arm and found a significant difference between the acupuncture and control groups (WMD 23.34, 95% CI 10.74 to 35.94; P<0.001). The fifth study used bioelectrical impedance spectroscopy to assess lymphoedema at several points on the arm before and after acupuncture; this study also reported a significant reduction in lymphoedema. The sixth study reported no significant difference in bioimpedance between the groups. Conclusions: The present meta-analysis and systematic review suggests that acupuncture is effective at reducing BCRL in patients after breast cancer treatment.

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Systematic Review and Meta-Analysis of Correlation of Progression-Free Survival-2 and Overall Survival in Solid Tumors

Frontiers in Oncology ◽

10.3389/fonc.2020.01349 ◽

2020 ◽

Vol 10 ◽

Author(s):

Simon Chowdhury ◽

Paul Mainwaring ◽

Liangcai Zhang ◽

Suneel Mundle ◽

Eneida Pollozi ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Solid Tumors ◽

Meta Analysis ◽

Progression Free Survival ◽

Free Survival

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A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4566 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4566-4566

Author(s):

S. Sym ◽

S. Park ◽

J. Park ◽

K. Kwon ◽

I. Jung ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Performance Status ◽

Objective Response ◽

Progression Free Survival ◽

Tolerability Profile ◽

Preliminary Results ◽

Weekly Docetaxel ◽

Randomized Phase Ii ◽

Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

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The Effectiveness and Safety of Acupuncture for Patients with Chronic Urticaria: A Systematic Review

BioMed Research International ◽

10.1155/2016/5191729 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Qin Yao ◽

Shanshan Li ◽

Xiaoxu Liu ◽

Zongshi Qin ◽

Zhishun Liu

Keyword(s):

Systematic Review ◽

Relative Risk ◽

Chronic Urticaria ◽

Primary Outcome ◽

Meta Analysis ◽

Symptom Improvement ◽

Control Groups ◽

Level Of Evidence ◽

Randomized Controlled ◽

Significant Difference

Background. Acupuncture might have effectiveness in relieving the symptoms of chronic urticaria. There are currently no systematic reviews of acupuncture for chronic urticaria published in English.Objective. We conducted a systematic review to assess the effectiveness and safety of acupuncture for chronic urticaria.Methods. A systematic review and meta-analysis of randomized, controlled trials were performed. The primary outcome was global symptom improvement.Results. We included 6 studies with 406 participants. Three trials showed significant difference between acupuncture and drugs in global symptom improvement (relative risk 1.37; 95% CI 1.11–1.70;P=0.003). As an adjuvant to medication, acupuncture was also beneficial for global symptom improvement (relative risk 1.77; 95% CI 1.41–2.22;P<0.01). There were no severe adverse events related to acupuncture.Limitations. Some methodological limitations were observed. The overall risk of bias in the 6 included trials was high and all included RCTs were conducted in China and published in Chinese. Besides, the lack of proper control groups and the use of different rating methods and cut-offs in the included trials also made the evidence of this review limited.Conclusions. Acupuncture might be effective and safe for chronic urticaria in relieving symptoms, based on a low level of evidence. To draw a reliable conclusion, more high quality trials are needed in the future. This trial is registered with PROSPEROCRD42015015702.

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Efficacy and safety of bevacizumab in the treatment of adult gliomas: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2021-048975 ◽

2021 ◽

Vol 11 (12) ◽

pp. e048975

Author(s):

Huan Wang ◽

Jianxin Guo ◽

Tianze Wang ◽

Kai Wang ◽

Zhuojun Wu ◽

...

Keyword(s):

Systematic Review ◽

Large Scale ◽

Meta Analysis ◽

Progression Free Survival ◽

Optimal Dose ◽

Secondary Outcome ◽

Efficacy And Safety ◽

Free Survival ◽

Significant Difference ◽

Clinical Centre

ObjectiveTo assess the efficacy and safety of bevacizumab (BEV) in patients with glioma.DesignSystematic review and meta-analysis.ParticipantsAdults aged 18 years and above, whose histology was confirmed to be malignant glioma.Primary and secondary outcome measuresThe main indicators included progression-free survival (PFS) rate and overall survival (OS) rate, and the secondary indicators were adverse reactions.ResultsA total of 11 clinical centre trials were included in this study for meta-analysis, including 2392 patients. The results of the meta-analysis showed that the median PFS rate of the BEV group was significantly higher than that of the non-BEV group (p<0.00001). When comparing PFS between two groups, we found that the PFS in the BEV group was higher than that in the non-BEV group at 6 months (OR 3.31, 95% CI 2.74 to 4.00, p<0.00001), 12 months (OR 2.05, 95% CI 1.70 to 2.49, p<0.00001) and 18 months (OR 1.31, 95% CI 1.02 to 1.69, p=0.03). But at 24 months (OR 0.83, 95% CI 0.50 to 1.37, p=0.47), there was no significant difference between the two groups. At 30 months (OR 0.62, 95% CI 0.39 to 0.97, p=0.04), the PFS of the BEV group was lower than that of the non-BEV group. Moreover, The results showed that BEV had no significant effect on improving OS, but the adverse reaction in BEV group was significantly higher than that in non-BEV group.ConclusionThe evidence suggests that BEV can significantly prolong the PFS of patients with glioma within 18 months and shorten the PFS of patients after 30 months. This limitation may be related to the subgroup of patients, the change of recurrence mode, the optimal dose of drug, the increase of hypoxia, the enhancement of invasiveness and so on. Therefore, it is necessary to carry out more samples and higher quality large-scale research in the future.

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Safety and Efficacy of Ginkgo-Damole and Nitroglycerin or Sodium Nitroprusside on Hypertensive Cerebropathies: A Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5713796 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Li Peng ◽

Wei-kun Zhao ◽

Tong-tong Xu ◽

Qi Wu ◽

Pan Lu ◽

...

Keyword(s):

Blood Pressure ◽

Sodium Nitroprusside ◽

Meta Analysis ◽

Control Group ◽

Clinical Effects ◽

Observation Group ◽

Control Groups ◽

Safety And Efficacy ◽

Significant Difference ◽

And Control

Objective. To systematically evaluate the safety and efficacy of ginko-damole combined with nitroglycerin or unitary sodium nitroprusside on hypertensive cerebropathy. Methods. Four Chinese databases (VIP, CBM, Wanfang database, and CNKI database) and three English databases (Cochrane, PubMed, and EMBASE) were used to screen randomised controlled trials (RCTs) on treatments of hypertensive cerebropathy using both ginko-damole and nitroglycerin or unitary sodium nitroprusside. Outcomes included clinical effect, blood pressure after treatment, and adverse effects. These indicators were then analysed statistically using the RevMan 5.3 and Stata 12.0 software. Results. Altogether, 16 RCTs including 1507 patients with hypertensive cerebropathy were included in the present meta-analysis, of which, 755 patients treated with combined ginko-damole and nitroglycerin were included in the observation group and 752 patients treated with sodium nitroprusside were included in the control group. The curative effect of the observation group was significantly better than that of the control group (RR: 1.115 [1.077, 1.155], p<0.05). DBPs of the observation and control groups were both lower after treatment, and no significant difference was observed between the observation and control groups (MD: −1.072 [−2.578, 0.434], p>0.05). SBPs in the observation group were significantly lower than those in the control group (MD: −2.842 [−5.222, −0.462], p<0.05). The probability of adverse response in both groups did not differ significantly (RR: 0.752 [0.412, 1.374], p>0.05). Conclusion. Compared with sodium nitroprusside, the combined ginkgo-damole and nitroglycerin could better control blood pressure in patients with hypertensive cerebropathy and showed enhanced clinical effects and improved safety. However, due to poor quality of the included studies, results of the present meta-analysis should be confirmed by more stringent RCTs.

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