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
- Chemotherapy, Adjuvant methods MeSH
- Immune Checkpoint Inhibitors * therapeutic use pharmacology MeSH
- Neoplasm Invasiveness MeSH
- Carcinoma, Transitional Cell drug therapy pathology MeSH
- Humans MeSH
- Urinary Bladder Neoplasms drug therapy pathology MeSH
- Network Meta-Analysis as Topic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Systematic Review MeSH
Karcinom endometria je obvykle diagnostikován v časném stadiu a po primární operační a následné adjuvantní onkologické léčbě má relativně dobrou prognózu. V případě lokální či regionální recidivy v oblasti pánve lze často účinně aplikovat záchrannou léčbu, ať už operační, či léčbu zářením. Pokud ale karcinom endometria recidivuje tak, že jej nelze řešit lokální záchrannou léčbou, nebo pokud metastazuje do vzdálených lokalit, je situace už mnohem vážnější. Díky molekulárně genetickým poznatkům dnes dovedeme nádory endometria lépe kategorizovat a také lépe předpovědět léčebnou odpověď nejen na chemoterapii, ale především na stále rychleji se rozvíjející imunoterapii cílenou na receptor programované buněčné smrti 1 (programmed cell death protein 1, PD-1) a jeho ligandy. Dostarlimab je prvním plně hrazeným tzv. „checkpoint inhibitorem“ v první linii léčby pacientek s rekurentním či metastazujícím MMR (mismatch repair) deficientním karcinomem endometria.
Endometrial cancer is usually diagnosed at an early stage and has a relatively good prognosis after primary surgery and subsequent adjuvant oncological treatment. In the case of local or regional recurrence in the pelvic region, salvage treatment, either surgery or radiation therapy, can often be effectively applied. However, if the endometrial cancer recurs so that it cannot be managed with local salvage treatment, or if it metastasises to distant sites, the situation is much more serious. Thanks to molecular genetic knowledge, we can now better categorize endometrial tumors and more accurately predict the therapeutic response not only to chemotherapy, but also to the rapidly developing immunotherapy targeting the programmed cell death protein 1 (PD-1) receptor and its ligands. Dostarlimab is the first fully reimbursed “checkpoint inhibitor” in the first-line treatment of patients with recurrent or metastatic MMR (mismatch repair) deficient endometrial cancer.
Nivolumab je průlomový onkologický lék patřící mezi inhibitory kontrolních bodů, který cílí na receptor programované buněčné smrti 1 (programmed cell death protein 1, PD-1). Jeho účinnost byla prokázána jak v monoterapii, tak v kombinaci s chemoterapií u mnoha typů onkologických diagnóz, včetně uroteliálního karcinomu. V léčbě metastazujícího uroteliálního karcinomu se nivolumab ukázal jako významný doplněk ke standardní chemoterapii, zejména u pacientů s pozitivní expresí ligandu programované buněčné smrti 1 (programmed cell death-ligand 1, PD-L1) a postižením lymfatických uzlin, kde významně prodlužuje celkové přežití a dobu bez progrese onemocnění. V adjuvantní léčbě nivolumab přináší prokazatelný benefit u pacientů po radikální operaci s vysokým rizikem relapsu. Studie prokázaly jeho schopnost prodloužit dobu do přežití bez známek onemocnění (disease free survival, DFS) a bez vzdálených metastáz (distant metastasis free survival, DMFS), přičemž jeho účinek je nejvýraznější u PD-L1 pozitivních pacientů.
Nivolumab is a breakthrough cancer drug belonging to the class of checkpoint inhibitors that targets the programmed cell death protein 1 receptor (PD-1). Its efficacy has been demonstrated both in monotherapy and in combination with chemotherapy in many types of cancer, including urothelial carcinoma. In the treatment of metastatic urothelial carcinoma, nivolumab has proven to be an important adjunct to standard chemotherapy, particularly in patients with positive programmed cell death-ligand 1 (PD-L1) expression and lymph node involvement, where it significantly prolongs overall survival and progression free survival. In adjuvant therapy, nivolumab provides a demonstrable benefit in patients after radical surgery with a high risk of relapse. Studies have demonstrated its ability to prolong disease free survival (DFS) and distant metastasis free survival (DMFS), with its effect being most pronounced in PD-L1 positive patients.
Spinocelulární karcinom kůže (cutaneous squamous cell carcinoma, cSCC) je jedním z nejčastějších kožních nádorů. Hlavní léčbou cSCC je chirurgický zákrok. Nicméně neoperabilní nebo metastazující cSCC zůstává neléčitelný. S nástupem imunoterapie se dostaly do popředí při léčbě těchto forem onemocnění checkpoint inhibitory, jako je cemiplimab. Cemiplimab je lék modulující imunitu, který se zaměřuje na receptor PD-1. Dosavadní výsledky ukazují nejen dobrou léčebnou odpověď, ale také dlouhodobou účinnost. Následující kazuistika dokazuje účinnost cemiplimabu i u zdánlivě neřešitelných případů.
Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The primary treatment for cSCC is surgical intervention. However, inoperable or metastatic cSCC remains difficult to treat. With the advent of immunotherapy, checkpoint inhibitors, such as cemiplimab, have become prominent in the treatment of these forms of the disease. Cemiplimab is an immune-modulating drug that targets the PD-1 receptor. Current results indicate not only a good therapeutic response but also long-term efficacy. The following case study demonstrates the effectiveness of cemiplimab even in seemingly intractable cases.
Immune checkpoints are critical in modulating immune responses and maintaining self-tolerance. Cancer cells can exploit these mechanisms to evade immune detection, making immune checkpoints attractive targets for cancer therapy. The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer treatment, with monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1 demonstrating clinical success. However, challenges such as immune-related adverse events, primary and acquired resistance, and high treatment costs persist. To address these challenges, it is essential to explore alternative strategies, including small-molecule and peptide-based inhibitors, aptamers, RNA-based therapies, gene-editing technologies, bispecific and multispecific agents, and cell-based therapies. Additionally, innovative approaches such as lysosome-targeting chimeras, proteolysis-targeting chimeras, and N-(2-hydroxypropyl) methacrylamide copolymers are emerging as promising options for enhancing treatment effectiveness. This review highlights significant advancements in the field, focusing on their clinical implications and successes.
- MeSH
- Adenocarcinoma of Lung drug therapy MeSH
- Diagnosis, Differential MeSH
- Adrenal Cortex Hormones pharmacology therapeutic use MeSH
- Immune Checkpoint Inhibitors adverse effects MeSH
- Colitis * chemically induced MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions drug therapy MeSH
- Nivolumab adverse effects MeSH
- Diarrhea * etiology MeSH
- Intestine, Large pathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Brentuximab Vedotin therapeutic use MeSH
- Hodgkin Disease diagnosis therapy MeSH
- Immunotherapy methods MeSH
- Immune Checkpoint Inhibitors therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Drug Therapy, Combination MeSH
- Response Evaluation Criteria in Solid Tumors MeSH
- Humans MeSH
- Recurrence MeSH
- Risk Factors MeSH
- Neoplasm Staging MeSH
- Stem Cell Transplantation MeSH
- Risk Adjustment MeSH
- Check Tag
- Humans MeSH
Východiska: Protinádorová imunoterapie je již standardem léčby nemalobuněčného karcinomu plic (non-small cell lung cancer – NSCLC) a to nejen u metastatického, ale i lokálně pokročilého onemocnění a také časných, operabilních stadií. Cíl: Článek podává přehled aktualizovaných výsledků studií EMPOWER-Lung 1 a EMPOWER-Lung 3. Ve studiích byla hodnocena účinnost cemiplimabu (monoklonální protilátky, která se váže na receptor programované buněčné smrti – PD-1) u pacientů s metastatickým a lokálně pokročilým NSCLC, kteří nejsou kandidáti operace a chemoradiace. Také uvádíme zkušenosti z našeho pracoviště, kde byl cemiplimab podán v monoterapii u pacientů s vysokou expresí ligandu PD-L1. Závěr: Cemiplimab prokázal účinnost v monoterapii u pacientů s NSCLC exprimujícím PD-L1 u ≥ 50 % nádorových buněk a v kombinaci s chemoterapií na bázi platinového dubletu při expresi PD-L1 u ≥ 1 % nádorových buněk v první linii léčby metastatického, ale také neresekovatelného lokálně pokročilého onemocnění, nevhodného pro definitivní chemoradiaci. Pro tyto pacienty je cemiplimab novou léčebnou možností.
Background: Immuno-oncotherapy is already the standard treatment for non-small cell lung cancer (NSCLC), not only for metastatic disease, but also for locally advanced disease as well as early, operable stages. Aim: The article provides an overview of the updated results of the EMPOWER-Lung 1 and EMPOWER-Lung 3 studies. The studies evaluated the efficacy of cemiplimab (a monoclonal antibody that binds to the programmed cell death receptor – PD-1) in patients with metastatic and locally advanced NSCLC who are not surgery and chemoradiation candidates. We also present the experience from our institution, when cemiplimab was administered as monotherapy in patients with high PD-L1 ligand expression. Conclusion: Cemiplimab demonstrated efficacy as monotherapy in patients with NSCLC expressing PD-L1 in ≥ 50% of tumor cells and in combination with platinum-doublet chemotherapy when expressing PD-L1 in ≥ 1% of tumor cells in the first-line treatment of metastatic but also unresectable locally advanced disease unsuitable for definitive chemoradiation, demonstrating a new treatment option for these patients.
- Keywords
- cemiplimab, EMPOWER-Lung 1, EMPOWER-Lung 3,
- MeSH
- Antibodies, Monoclonal, Humanized pharmacology therapeutic use MeSH
- Immunotherapy methods MeSH
- Immune Checkpoint Inhibitors * pharmacology classification therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Carcinoma, Non-Small-Cell Lung * diagnosis drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
