BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.
- MeSH
- Anilides * therapeutic use pharmacology administration & dosage MeSH
- Axitinib * therapeutic use pharmacology administration & dosage MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use pharmacology administration & dosage MeSH
- Carcinoma, Renal Cell * drug therapy mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms * drug therapy pathology mortality MeSH
- Nivolumab * therapeutic use pharmacology administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use MeSH
- Pyridines therapeutic use MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
- Keywords
- kabozantinib,
- MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Carcinoma, Renal Cell * drug therapy MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * drug therapy MeSH
- Lung Neoplasms drug therapy secondary MeSH
- Antineoplastic Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Aged MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kabozantinib, Cabometyx,
- MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Carcinoma, Renal Cell * surgery drug therapy MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * surgery drug therapy MeSH
- Lung Neoplasms drug therapy secondary MeSH
- Antineoplastic Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Aged MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kabozantinib,
- MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Carcinoma, Renal Cell * surgery drug therapy MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * surgery drug therapy MeSH
- Lung Neoplasms drug therapy secondary MeSH
- Brain Diseases chemically induced drug therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Nivolumab administration & dosage pharmacology adverse effects therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Aged MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kabozantinib,
- MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * surgery drug therapy MeSH
- Lung Neoplasms drug therapy secondary MeSH
- Antineoplastic Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kabozantinib,
- MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Adult MeSH
- Carcinoma, Renal Cell * surgery drug therapy MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * surgery drug therapy MeSH
- Lung Neoplasms surgery drug therapy secondary MeSH
- Pancreatic Neoplasms surgery drug therapy secondary MeSH
- Antineoplastic Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kabozantinib, studie CheckMate 9ER,
- MeSH
- Survival Analysis MeSH
- Anilides administration & dosage pharmacology therapeutic use MeSH
- Progression-Free Survival MeSH
- Carcinoma, Renal Cell * drug therapy MeSH
- Clinical Studies as Topic MeSH
- Clinical Trials, Phase III as Topic MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * drug therapy MeSH
- Nivolumab pharmacology therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Pyridines administration & dosage pharmacology therapeutic use MeSH
- Receptor Protein-Tyrosine Kinases administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
V indikaci metastatického GIST zůstávají standardem preparáty imatinib, sunitinib, regorafenib. Avapritinib (nový TK-inhibitor) je nově schválen v indikaci 1. linie metastatického GIST s mutací PDGFR D842, ale neprokázal superioritu oproti regorafenibu v celé populace GIST. Mezi další zajímavé tyrosinkinázové inhibitory patří kabozantinib, pazopanib, ripretinib. Data o efektivitě BRAF blokátorů a imunoterapii anti-PD-1 preparáty jsou zatím velmi omezená. Znovunasazení imatinibu po selhání předchozí léčby imatunibem, sunitinibem a regorafenibem se zdá být efektní jen minimálně. Doporučený standard 3leté adjuvantní léčby imatinibemu pacientů po resekci GIST vysokého rizika nezměnily ani výsledky studie PERSIST s aplikovaným imatinibem v adjuvantní indikaci po dobu 5 let.
Imatinib, sunitinib, and regorafenib have remained the standard therapy for metastatic GIST. Avapritinib (a novel TK inhibitor) has been newly approved as the first-line treatment of metastatic GIST with a PDGFR D842 mutation, but has not been shown to be superior compared with regorafenib in the entire GIST population. Other interesting tyrosine kinase inhibitors include cabozantinib, pazopanib, and ripretinib. Data on the efficacy of BRAF inhibitors and immunotherapy with anti-PD-1 drugs have been limited so far. Repeated administration of imatinib after failure of previous treatment with imatinib, sunitinib, and regorafenib appears to have a minimum effect only. The recommended standard of 3-year adjuvant therapy with imatinib in patients after high-risk GIST resection has remained unchanged by the results of the PERSIST clinical trial with a 5-year administration of adjuvant imatinib.
- Keywords
- regorafenib, cabozantinib, avapritinib, ripretinib,
- MeSH
- Anilides administration & dosage therapeutic use MeSH
- Phenylurea Compounds administration & dosage therapeutic use MeSH
- Gastrointestinal Stromal Tumors * therapy MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Imatinib Mesylate administration & dosage therapeutic use MeSH
- Humans MeSH
- Urea analogs & derivatives MeSH
- Naphthyridines administration & dosage therapeutic use MeSH
- Antineoplastic Agents MeSH
- Pyrazoles administration & dosage therapeutic use MeSH
- Pyridines administration & dosage therapeutic use MeSH
- Pyrroles administration & dosage therapeutic use MeSH
- Sunitinib administration & dosage therapeutic use MeSH
- Triazines administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Česká republika celosvětově dosahuje prvenství v incidenci zhoubných nádorů ledvin. Přibližně 70 % zhoubných nádorů ledvin představuje světlobuněčný renální karcinom, který je spojen s dysfunkcí genu von Hippel-Lindau (VHL). Tato porucha je spojena s akumulací hypoxií indukovatelného faktoru (hypoxia-inducible factor, HIF), v jejímž důsledku dochází k podobným metabolickým jevům jako při hypoxii. Výsledkem je indukce vaskulárního endoteliálního růstového faktoru (vascular endothelial growth factor, VEGF) s následnou stimulací angiogeneze. Racionálním podkladem terapie je proto inhi - bice angiogeneze. Podle aktuální úhradové vyhlášky mají největší význam v léčbě první linie metastazujícího světlobuněčného renálního karcinomu inhibitory receptoru vaskulárního endoteliálního růstového faktoru (vascular endothelial growth factor receptor, VEGFR) sunitinib a pazopanib. U většiny pacientů dochází ale postupně k progresi onemocnění. Do druhé linie lze aktuálně indikovat novější inhibitor VEGFR cabozantinib, který působí i na jiné signální dráhy (MET, AXL). Tato skutečnost dovoluje překonávat rezistenci na předchozí inhibitory VEGFR. Důkazem jsou výsledky studie METEOR, kde cabozantinib prokázal ve srovnání s everolimem významné prodloužení přežití bez známek progrese, celkové přežití i dosažení léčebné odpovědi po předchozí léčbě inhibitory VEGFR. Na našem pracovišti jsme cabozantinib začali v klinické praxi používat od roku 2018. Níže popisujeme kazuistiku pacienta léčeného právě cabozantinibem.
The Czech Republic is the world leader in the incidence of kidney cancer worldwide. Approximately 70% of renal cancers are clear cell renal, which is associated with von Hippel-Lindau (VHL) gene dysfunction. This disorder is associated with the accumulation of hypoxia-inducible factor (HIF), which results in similar metabolic events as in hypoxia. The result is the induction of vascular endothelial growth factor (VEGF) with subsequent stimulation of angiogenesis. Inhibition of angiogenesis is therefore a rational basis for therapy. According to the current reimbursement decree, sunitinib and pazopanib inhibitors are of the greatest importance in the first-line treatment of metastatic clear cell renal cell carcinoma of the vascular endothelial growth factor receptor (VEGFR). In most patients, however, the disease gradually progresses. The newer VEGFR inhibitor cabozantinib, which also acts on other signaling pathways (MET, AXL), can currently be indicated in the second line. This fact makes it possible to overcome resistance to previous VEGFR inhibitors. This is evidenced by the results of the METEOR study, where cabozantinib showed a significant prolongation of progression-free survival, overall survival and response to previous treatment with VEGFR inhibitors compared to everolimus. We started using cabozantinib in clinical practice at our workplace in 2018. Below we describe the case report of a patient treated with cabozantinib.
- Keywords
- cabozantinib,
- MeSH
- Anilides administration & dosage therapeutic use MeSH
- Hypertension chemically induced MeSH
- Carcinoma, Renal Cell * diagnosis therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis diagnosis therapy MeSH
- Receptors, Vascular Endothelial Growth Factor * antagonists & inhibitors MeSH
- Sunitinib therapeutic use MeSH
- Hand-Foot Syndrome etiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
BACKGROUND: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 'CaboGIST' assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib. METHODS: In this multi-center, open label, single arm phase II study, eligible GIST patients received oral cabozantinib (60 mg) once daily. Primary end-point was the progression-free survival rate at 12 weeks assessed by the local investigator per Response Evaluation Criteria in Solid Tumours 1·1. If at least 21 of the first 41 eligible and evaluable patients were progression-free at week 12, the activity of cabozantinib was sufficient to warrant further exploration according to the A'Hern one-stage study design. FINDINGS: A total of 50 eligible patients started treatment between 02/2017 and 08/2018, including four (8%) still continuing cabozantinib at clinical cut-off (09/2019). The number of 3-weekly treatment cycles ranged from 1 to 30. Among the first 41 eligible and evaluable patients, 24 were progression-free at week 12 (58·5%, 95% confidence interval [CI] 42·0-74·0%). Among all 50 patients, 30 were progression-free at week 12 (60%, 95% CI 45-74%). Seven patients achieved a partial response (14%, 95% CI 6-27%), and 34 had stable disease (68%, 95% CI 53-80%) as best response. Progression was seen in eight patients (16%, 95% CI 7-29%), and one was not evaluable. Disease control was achieved in 41 patients (82%, 95% CI 69-91%). Median progression-free survival was 5·5 months (95% CI 3·6-6·9). The most common adverse events were diarrhoea (76%), palmar-plantar erythrodysesthesia syndrome (60%), fatigue (50%), hypertension (42%), weight loss (40%) and oral mucositis (30%), with 32 (64%) patients requiring dose reductions, 27 (54%) having treatment interruptions and no cabozantinib-related deaths observed. INTERPRETATION: EORTC 1317 met its primary end-point, with 24/41 patients being progression-free at week 12 of treatment. The objective response was 14% with an encouraging disease control rate of 82%. Results of this trial confirm preclinical findings and warrant further exploration of cabozantinib in GIST. CLINICAL TRIAL NUMBERS: EORTC 1317, NCT02216578, EudraCT 2014-000501-13.
- MeSH
- Anilides administration & dosage MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Adult MeSH
- Gastrointestinal Neoplasms drug therapy pathology MeSH
- Gastrointestinal Stromal Tumors drug therapy secondary MeSH
- Imatinib Mesylate administration & dosage MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyridines administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sunitinib administration & dosage MeSH
- Salvage Therapy * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
