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The Journal of Urology Sep 2023There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic therapies. We aimed to analyze and compare the efficacy of combination systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with or without visceral metastasis.
MATERIALS AND METHODS
Three databases were queried in July 2022 for randomized, controlled trials analyzing metastatic prostate cancer patients treated with combination systemic therapy (androgen receptor signaling inhibitor and/or docetaxel plus androgen deprivation therapy) to standard of care. We analyzed the association between presence of visceral metastases and efficacy of systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients. The main and secondary outcomes of interest were overall survival and progression-free survival, respectively. Formal meta-analysis using fixed-effect model and network meta-analysis using random-effect model were conducted. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines.
RESULTS
Overall, 12 and 8 randomized, controlled trials were included for systematic review and meta-analyses/network meta-analyses, respectively. In metastatic hormone-sensitive prostate cancer patients, adding androgen receptor signaling inhibitor to standard of care improved overall survival in patients with visceral metastasis (pooled HR: 0.77, 95% CI: 0.64-0.94) as well as in those without (pooled HR: 0.66, 95% CI: 0.60-0.72; no differences in both across- and within-trial approach; = .13 and = .06, respectively). On the other hand, the progression-free survival benefit from androgen receptor signaling inhibitor + androgen deprivation therapy was significantly lower in patients with visceral metastasis using across-trial approach ( = .03), while it did not reach statistical significance using within-trial approach ( = .14). Analysis of treatment ranking in metastatic hormone-sensitive prostate cancer showed that darolutamide + docetaxel + androgen deprivation therapy had the highest likelihood of improved overall survival irrespective of visceral metastasis. In post-docetaxel metastatic castration-resistant prostate cancer patients, adding androgen receptor signaling inhibitor to androgen deprivation therapy significantly improved overall survival in both patients with visceral metastasis (pooled HR: 0.79, 95% CI: 0.63-0.98) and those without (pooled HR: 0.63, 95% CI: 0.55-0.72). No randomized, controlled trials reported the differential oncologic outcomes stratified by lung vs liver metastases.
CONCLUSIONS
Despite aggressive clinical behavior and worse trajectory of metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with visceral metastasis, the effectiveness of novel systemic therapies is similar in both metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients with and without visceral metastasis. Further well-designed studies with detailed visceral metastatic sites and number will enrich the clinical decision-making.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Prostatic Neoplasms, Castration-Resistant; Network Meta-Analysis; Androgen Antagonists; Receptors, Androgen; Androgens; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Metastasis
PubMed: 37339479
DOI: 10.1097/JU.0000000000003594 -
Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
Prostate Cancer and Prostatic Diseases Dec 2023Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS).
METHODS
As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations.
RESULTS
Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25-79%), 64% (CI: 43-80%) and 55% (CI: 36-73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26-0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82-2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients.
CONCLUSIONS
Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms, Castration-Resistant; BRCA1 Protein; Treatment Outcome; BRCA2 Protein; Nitriles; Retrospective Studies
PubMed: 36509931
DOI: 10.1038/s41391-022-00626-2 -
Clinical and Experimental Medicine Oct 2023Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of... (Meta-Analysis)
Meta-Analysis Review
Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45-0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38-0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43-0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40-0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37-0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23-0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37-0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19-0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable.
Topics: Humans; Female; Triple Negative Breast Neoplasms; Platinum; Myalgia; Breast Neoplasms; Paclitaxel; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Neutropenia; Anthracyclines; Arthralgia; Anemia; Neoadjuvant Therapy
PubMed: 36422737
DOI: 10.1007/s10238-022-00940-y -
Journal of Endovascular Therapy : An... Apr 2024Local Liquid drug (LLD) delivery devices have recently emerged as a novel approach to treat peripheral arterial disease. This systemic review aims to identify and... (Review)
Review
OBJECTIVE
Local Liquid drug (LLD) delivery devices have recently emerged as a novel approach to treat peripheral arterial disease. This systemic review aims to identify and evaluate the clinical utility of the most commonly used delivery devices.
METHODS
A systemic review was performed using the Medical Subjects Heading terms of "drug delivery," "liquid," "local," and "cardiovascular disease" in PubMed, Google Scholar, and Scopus.
RESULTS
Four commonly used delivery devices were identified, including (1) the Bullfrog Micro-Infusion Device, (2) the ClearWay RX Catheter, (3) the Occlusion Perfusion Catheter, and (4) the Targeted Adjustable Pharmaceutical Administration. All have shown to successfully deliver liquid therapeutic into the target lesion and have exhibited favorable safety and efficacy profiles in preclinical and clinical trials. The LLD devices have the ability to treat very long or multiple lesions with a single device, providing a more economical option. The safety profile in LLD clinical studies is also favorable in view of recent concerns regarding adverse events with crystalline-paclitaxel-coated devices.
CONCLUSION
There is clear clinical evidence to support the concept of local liquid delivery to treat occlusive arterial disease.
CLINICAL IMPACT
The 'leave nothing behind' strategy has been at the forefront of the most recent innovations in the field of interventional cardiology and vascular interventions. Although drug coated balloons have overcome limitations associated with plain old balloon angioplasty and peripheral stents, recent safety concerns and cost considerations have impacted their usage. In this review, various liquid drug delivery devices are presented, showcasing their capabilities and success in both preclinical and clinical settings. These innovative liquid delivery devices, capable of targeted delivery and their ability to be re-used for multiple treatment sites, may provide solutions for current unmet clinical needs.
Topics: Humans; Popliteal Artery; Femoral Artery; Treatment Outcome; Drug-Eluting Stents; Cardiovascular Agents; Peripheral Arterial Disease; Paclitaxel; Angioplasty, Balloon; Coated Materials, Biocompatible
PubMed: 36052425
DOI: 10.1177/15266028221120755 -
Cardiovascular Drugs and Therapy Aug 2023Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and... (Review)
Review
PURPOSE
Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and dexamethasone in the treatment and prophylaxis of PPS.
METHODS
Literature research was carried out using PubMed. Studies investigating ≥ 10 patients with clinically PPS treated with colchicine, dexamethasone, and indomethacin and compared with placebo were included. Animal or in vitro experiments, studies on < 10 patients, case reports, congress reports, and review articles were excluded. Cochrane risk-of-bias tool for randomized trials (RoB2) was used for the quality assessment of studies.
RESULTS
Seven studies were included. Among studies with postoperative colchicine treatment, two of them demonstrated a significant reduction of PPS. In the single pre-surgery colchicine administration study, a decrease of PPS cases was registered. Indomethacin pre-surgery administration was linked to a reduction of PPS. No significant result emerged with preoperative dexamethasone intake.
CONCLUSION
Better outcomes have been registered when colchicine and indomethacin were administered as primary prophylactic agents in preventing PPS and PE. Further RCT studies are needed to confirm these results.
Topics: Humans; Pericardiectomy; Postpericardiotomy Syndrome; Cardiac Surgical Procedures; Colchicine; Indomethacin; Dexamethasone
PubMed: 34546452
DOI: 10.1007/s10557-021-07261-4