CONTEXT: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. OBJECTIVE: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. EVIDENCE ACQUISITION: In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. EVIDENCE SYNTHESIS: Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. CONCLUSIONS: Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.
- MeSH
- adjuvantní chemoterapie metody MeSH
- inhibitory kontrolních bodů * terapeutické užití farmakologie MeSH
- invazivní růst nádoru MeSH
- karcinom z přechodných buněk farmakoterapie patologie MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie patologie MeSH
- síťová metaanalýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
BACKGROUND: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. PATIENTS AND METHODS: VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. RESULTS: The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. CONCLUSION: Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.
- MeSH
- adenokarcinom * patologie farmakoterapie terapie MeSH
- adjuvantní chemoterapie metody MeSH
- dospělí MeSH
- gastrektomie MeSH
- gastroezofageální junkce * patologie MeSH
- imunoterapie metody MeSH
- ipilimumab aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * patologie prevence a kontrola farmakoterapie epidemiologie MeSH
- nádory jícnu * patologie farmakoterapie terapie MeSH
- nádory žaludku * patologie farmakoterapie terapie chirurgie MeSH
- neoadjuvantní terapie * metody škodlivé účinky MeSH
- nivolumab aplikace a dávkování terapeutické užití MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
PURPOSE OF REVIEW: This review explores the potential role of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for oligometastatic bladder cancer (OMBC) treatment. We focused on extrapolating evidence from studies including lymph node-positive only and metastatic bladder cancer to address the key challenges and therapeutic strategies for OMBC. RECENT FINDINGS: Current evidence for NAC and RC in OMBC is limited, with most data derived from studies in locally advanced bladder cancer. NAC has shown efficacy in downstaging and improving survival in patients with locally advanced disease, but its benefits in OMBC remain speculative. Additionally, diagnostic uncertainties, particularly regarding the inclusion of pelvic lymph nodes and the role of FDG-PET/CT, pose significant challenges to accurate staging and treatment decisions. Recent studies highlight the potential of metastasis-directed therapy, but uncertainties remain on patient selection and treatment protocols for OMBC. SUMMARY: There is need for prospective studies to evaluate neoadjuvant systemic treatments and RC specifically in OMBC. Moreover, resolving current diagnostic challenges is crucial to avoid undertreatment due to inaccurate staging. Until more concrete evidence emerges, changes to standard treatment protocols should be approached with caution and offered only within trials.
- MeSH
- adjuvantní chemoterapie metody MeSH
- cystektomie * metody MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- nádory močového měchýře * patologie terapie chirurgie MeSH
- neoadjuvantní terapie * metody MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Serózní tubární intraepiteliální karcinom (STIC) je považován za prekurzor high grade serózního karcinomu pánve (HGSC), který zahrnuje karcinomy ovaria, tuby a peritonea. STIC je brzkou morfologicky rozpoznatelnou lézí v patogenezi HGSC a je nalézán převážně v distální části vejcovodu. I přes velký pokrok v objasnění patogeneze ovariálních karcinomů a zavedení nových patologických postupů při diagnostice prekurzorových lézí HGSC zůstává na tomto poli mnoho nezodpovězených otázek.
Serous tubal intraepithelial carcinoma (STIC) is considered as a precursor of high-grade serous carcinoma of the pelvis (HGSC), which includes ovarian, tubal and peritoneal carcinomas. STIC is an early morphologically recognizable lesion in the pathogenesis of HGSC and is found predominantly in the distal part of the fallopian tube. Despite a great progress in elucidating the pathogenesis of ovarian carcinomas and the introduction of new pathological procedures for the diagnosis of precursor lesions of HGSC, there remain many unanswered questions.
- MeSH
- adjuvantní chemoterapie metody MeSH
- časná detekce nádoru metody MeSH
- genetická predispozice k nemoci MeSH
- gynekologické chirurgické výkony metody MeSH
- karcinom in situ diagnóza patologie terapie MeSH
- lidé MeSH
- nádory cystické, mucinózní a serózní chirurgie diagnóza patologie MeSH
- nádory vaječníků diagnóza patologie terapie MeSH
- nádory vejcovodů * diagnóza patologie terapie MeSH
- Check Tag
- lidé MeSH
Ovariální karcinom představuje nejčastější příčinu úmrtí z gynekologických malignit. U dvou třetin pacientek je nemoc diagnostikována v pokročilém stadiu s peritoneální karcinomatózou. Základem léčby je v současné době primární cytoredukční výkon s cílem dosažení mikroskopického rezidua s následnou systémovou léčbou chemoterapií. V případech, kdy není možné dosáhnout optimální cytoredukci, je alternativou podání neoadjuvantní chemoterapie s následnou operací. V současné době lze pozorovat rostoucí zájem o zhodnocení potenciálního přínosu radikální cytoredukční operace v kombinaci s hypertermickou intraperitoneální chemoterapií (HIPEC) především v primární léčbě pokročilého ovariálního karcinomu. Nově jsou k dispozici výsledky III. fáze multicentrických prospektivních studií.
- MeSH
- adjuvantní chemoterapie metody MeSH
- cytoredukční chirurgie metody MeSH
- hypertermická intraperitoneální peroperační chemoterapie metody MeSH
- lidé MeSH
- lokální recidiva nádoru patologie terapie MeSH
- nádory vaječníků * diagnóza patologie terapie MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- dabrafenib, trametinib, studie COMBI-AD,
- MeSH
- adjuvantní chemoterapie * metody MeSH
- analýza přežití MeSH
- klinická studie jako téma MeSH
- kongresy jako téma MeSH
- lidé MeSH
- melanom * farmakoterapie sekundární MeSH
- metastázy nádorů farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
- Klíčová slova
- pembrolizumab,
- MeSH
- adjuvantní chemoterapie metody MeSH
- humanizované monoklonální protilátky farmakologie klasifikace terapeutické užití MeSH
- inhibitory kontrolních bodů * farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- melanom * diagnóza farmakoterapie MeSH
- nivolumab farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- souhrny MeSH
BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. METHODS: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. RESULTS: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. CONCLUSIONS: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).
- MeSH
- adjuvantní chemoterapie škodlivé účinky metody MeSH
- analýza přežití MeSH
- cisplatina aplikace a dávkování škodlivé účinky MeSH
- cystektomie * MeSH
- deoxycytidin * aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- gemcitabin MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky * aplikace a dávkování škodlivé účinky MeSH
- nádory močového měchýře * mortalita patologie terapie MeSH
- neoadjuvantní terapie škodlivé účinky metody MeSH
- protinádorové látky imunologicky aktivní * aplikace a dávkování škodlivé účinky MeSH
- protokoly protinádorové kombinované chemoterapie * aplikace a dávkování škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. METHODS: We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSIONS: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. RESEARCH SUPPORT: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
- MeSH
- adjuvantní chemoterapie metody MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory endometria * patologie farmakoterapie terapie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Klíčová slova
- pembrolizumab, durvalumab, atezolizumab, alectinib, osimertinib,
- MeSH
- adjuvantní chemoterapie metody MeSH
- cílená molekulární terapie * MeSH
- imunoterapie * MeSH
- inhibitory kontrolních bodů farmakologie terapeutické užití MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- nemalobuněčný karcinom plic * chirurgie farmakoterapie imunologie MeSH
- neoadjuvantní terapie metody MeSH
- nivolumab farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
