scholarly journals PD-1/PD-L1 Immune Checkpoint Inhibitors after Platinum-based Chemotherapy in Metastatic or Locally Advanced Urothelial Bladder Carcinoma: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Thara Tunthanathip ◽  
Tanan Bejrananda
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Cell Death ◽  
Bladder Carcinoma ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Second Line ◽  
Urothelial Bladder Carcinoma ◽  
Urothelial Bladder ◽  
Line Chemotherapy

Objective: This study aimed to assess the effect of anti-programmed cell death-1/programmed cell death-ligand-1 (PD-1/PD-L1) agents compared with second-line therapy in patients with metastatic or locally advanced urothelial bladder carcinoma following previous platinum-containing chemotherapy.Material and Methods: We systematically searched three electronic databases. The protocol of the study was registered in Prospero (CRD42019142494). Using the Grading of Recommendations Assessment, Development, and Evaluation approach, the certainty of evidence (CoE) was estimated.Results: The search results initially found 8168 publications. For qualitative synthesis, two publications were included. Pooled results indicated that patients treated with anti-PD-1/PD-L1 agents had significantly prolonged overall survival (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.7-0.9; I2 21.0%; moderate CoE). According to positive PD-L1 expression, PD-1/PD-L1 inhibitors had significantly more survival than chemotherapy (HR 0.75; 95% CI 0.5-0.9, I2 57.0%, low CoE). Furthermore, there was no significant difference in adverse events (AE) between the anti-PD-1/PDL1 agents and second-line chemotherapy (risk ratio 0.68; 95% CI 0.3-1.4; I2 97.0%, low CoE).Conclusion: The present meta-analysis and systematic review provide strong evidence that anti-PD-1/PD-L1 agents could improve overall survival and have similar results in AEs compared with second-line chemotherapy. Further studies will confirm the power of immunotherapy for the treatment of metastatic or locally advanced urothelial bladder carcinoma.

Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Setting ◽  
Line Chemotherapy

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.

scholarly journals Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1880
Author(s):  
Nanda Horeweg ◽  
Prachi Mittal ◽  
Patrycja L. Gradowska ◽  
Ingrid Boere ◽  
Supriya Chopra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Treatment Completion ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Hazard Ratios

Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Methods: PubMed, EMBASE and Web of Science were systematically searched for relevant prospective and retrospective studies. Two authors independently selected studies, extracted data and assessed study quality. Pooled hazard ratios for survival endpoints were estimated using random effect models. Weighted averages of treatment completion and toxicity rates were calculated and compared by the Fisher exact test. Results: The search returned 612 articles; 35 articles reporting on 29 different studies on adjuvant chemotherapy or immunotherapy were selected for systematic review. Twelve studies on an adjuvant platinum–pyrimidine antagonist or platinum–taxane were included for meta-analysis. The pooled hazard ratios for overall survival were 0.76 (99%CI: 0.43–1.34, p = 0.22) and 0.47 (99%CI: 0.12–1.86, p = 0.16) for the addition of, respectively, a platinum–pyrimidine antagonist or platinum–taxane to chemoradiation and brachytherapy. Completion rates were 82% (95%CI: 76–87%) for platinum–pyrimidine antagonist and 74% (95%CI: 63–85%) for platinum–taxane. Severe acute hematological and gastro-intestinal toxicities were significantly increased by adding adjuvant chemotherapy to chemoradiation and brachytherapy. Conclusions: The addition of adjuvant platinum–pyrimidine antagonist or platinum–taxane after chemoradiation and brachytherapy does not significantly improve overall survival, while acute toxicity is significantly increased. These adjuvant treatment strategies can therefore not be recommended for unselected patients with locally advanced cervical cancer.

Substaging of pT1 Urothelial Bladder Carcinoma Predicts Tumor Progression and Overall Survival

2021 ◽  
pp. 1-8
Author(s):  
Elisabeth Grobet-Jeandin ◽  
Gregory Johannes Wirth ◽  
Daniel Benamran ◽  
Amandine Dupont ◽  
Jean-Christophe Tille ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Progression ◽  
Bladder Carcinoma ◽  
Tumor Staging ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Rank Test ◽  
Progression Rate ◽  
Urothelial Bladder Carcinoma ◽  
Urothelial Bladder

<b><i>Introduction:</i></b> Limitations in tumor staging and the heterogeneous natural evolution of pT1 urothelial bladder carcinoma (UBC) make the choice of treatment challenging. We evaluated if histopathological substaging (pT1a, pT1b, and pT1c) helps predict disease recurrence, progression, and overall survival following transurethral resection of the bladder (TURB). <b><i>Methods:</i></b> We included 239 consecutive patients diagnosed with pT1 UBC at TURB in a single institution since 2001. Each sample was interpreted by our specialized uropathologists trained to subclassify pT1 stage. Three groups were distinguished according to the degree of invasion: T1a (up to the muscularis mucosae [MM]), T1b (into the MM), and T1c (beyond the MM). <b><i>Results:</i></b> T1 substaging was possible in 217/239 (90%) patients. pT1a, b, and c occurred in 124 (57), 59 (27), and 34 (16%), respectively. The median follow-up was 3.1 years, with a cumulative recurrence rate of 52%, progression rate of 20%, and survival rate of 54%. Recurrence was not significantly associated with tumor substage (<i>p</i> = 0.61). However, the Kaplan-Meier survival analysis showed a significantly higher progression rate among T1b (31) and T1c (26%) tumors than T1a (13%) (log-rank test: <i>p</i> = 0.001) stages. In a multivariable model including gender, age, ASA score, smoking, tumor grade, and presence of carcinoma in situ, T1 substage was the single variable significantly associated with progression-free survival (HR 1.7, <i>p</i> = 0.005). Nineteen patients (9%) needed radical cystectomy; among them, 12/19 (63%) had an invasive tumor. Overall survival was significantly associated with tumor substaging (<i>p</i> = 0.001). <b><i>Conclusion:</i></b> Histopathological substaging of pT1 UBC is significantly associated with tumor progression and overall survival and therefore appears to be a useful prognostic tool to counsel patients about treatment options.

Efficacy of adjuvant vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (VEGFRi) in renal cell carcinoma (RCC): A systematic review and meta-analysis.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 680-680
Author(s):  
Tobias Engel Ayer Botrel ◽  
Otávio Clark ◽  
Francisco Flávio Horta Bretas ◽  
Marcus V. Sadi ◽  
Ubirajara Ferreira ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Fixed Effect

680 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing the efficacy of adjuvant VEGFRi in locally advanced, non-metastatic clear renal-cell carcinoma (RCC). Methods:Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included studies that compared the addition of VEGFRi versus placebo, after nephrectomy. Analyzed endpoints were overall survival (OS) and disease-free survival (DFS). The data extracted from the studies were combined by using Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 121 references were identified and screened. The final analysis included 5 trials (S-TRAC, ATLAS, ASSURE, PROTECT and SORCE) comprising 6,128 patients that underwent previous nephrectomy for RCC. The DFS was similar in patients who received VEGFRi (fixed effect: HR=0.94, CI95%=0.87 to 1.03; p=0.19), with no heterogeneity (Chi2 = 4.33, df = 5 (P=0.50); I2 = 0%). Overall survival also was not statistically better in patients who received VEGFR inhibitors (HR=1.01, CI95%=0.90 to 1.15; p=0.84), with no heterogeneity (Chi2= 3.57, df = 5 (P=0.61); I2 = 0%). In the final combined analysis of the higher-risk disease group (pT3, pT4, or N+ disease), patients who received VEGFRi had a longer DFS (fixed effect: HR=0.85, CI95%=0.74 to 0.97; p=0.02), with no heterogeneity (Chi2 = 2.46, df = 3 (P=0.48); I2 = 0%). Overall survival was not statistically different for these higher-risk disease patients (fixed effect: HR=0.93, CI95%=0.74 to 1.16; p=0.5). Conclusions: This is the first meta-analysis including the five available RCTs in the literature (the previous meta-analysis reviewed only four), comparing adjuvant VEGFRi versus placebo in patients submitted to nephrectomy with a locally advanced, non-metastatic RCC. Adjuvant VEGFRi did not increase the OS in this group of patients. Amodest benefit of DFS with the use of adjuvant VEGFR inhibitors was restricted to patients with the highest risk of relapse.

scholarly journals FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

2020 ◽  
Vol 12 ◽  
pp. 175883592094797
Author(s):  
Francesca Foschini ◽  
Fabiana Napolitano ◽  
Alberto Servetto ◽  
Roberta Marciano ◽  
Eleonora Mozzillo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Optimal Sequence ◽  
Line Chemotherapy

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.

scholarly journals Urothelial bladder carcinoma metastasizing to the eye: A systematic review and case report

2018 ◽  
Author(s):  
Guido Giordano ◽  
Nunzio Olivieri ◽  
Mario D'Andrea ◽  
Tania Di Raimo ◽  
Erminia Manfrin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Case Report ◽  
Bladder Carcinoma ◽  
Urothelial Bladder Carcinoma ◽  
Urothelial Bladder
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