BACKGROUND AND OBJECTIVE: Adjuvant pembrolizumab significantly improved overall survival (OS) in renal cell carcinoma (RCC), but real-world data on sequential treatment are scarce. We sought to evaluate the clinical outcomes of first-line (1L) systemic therapy following adjuvant immune oncology (IO)-based regimens. METHODS: A retrospective study including patients with recurrent RCC following adjuvant IO across 29 international institutions was conducted. The primary endpoint was progression-free survival (PFS) on 1L systemic therapy estimated using the Kaplan-Meier method. Preplanned subanalyses of clinical outcomes by type of 1L systemic therapy, recurrence timing, and International Metastatic RCC Database Consortium (IMDC) risk groups were performed. Treatment-related adverse events leading to treatment discontinuation, dose reduction, or corticosteroid use were assessed. KEY FINDINGS AND LIMITATIONS: A total of 94 patients were included. Most received adjuvant pembrolizumab (n = 37, 39%), atezolizumab (n = 28, 30%), or nivolumab + ipilimumab (n = 15, 16%). The cohort included 49 (52%) patients who had recurrence within 3 mo of the last adjuvant IO dose, whereas 45 (48%) recurred beyond 3 mo. Bone metastases were significantly higher in tumors recurring at <3 mo (10/49, 20%) than those recurring at >3 mo (1/45, 2.2%; p = 0.008). Most patients received 1L vascular endothelial growth factor-targeted therapy (VEGF-TT; n = 37, 39%), IO + VEGF-TT (n = 26, 28%), or IO + IO (n = 12, 13%). The remaining underwent local therapy. The median follow-up for the 1L systemic therapy cohort was 15 mo. The 18-mo PFS and OS rates were 45% (95% confidence interval [CI]: 34-60) and 85% (95% CI: 75-95), respectively. Treatment-related adverse events occurred in 32 (42%) patients and included skin toxicity (n = 7, 9.2%), fatigue (n = 6, 7.9%), and diarrhea/colitis (n = 4, 5.3%). Limitations included selecting patients from large academic centers and the short follow-up period. CONCLUSIONS AND CLINICAL IMPLICATIONS: A subset of patients with recurrent RCC following adjuvant IO respond to systemic therapies, including VEGF-TT and IO-based regimens. Notably, patients with favorable-risk disease may derive more benefit from VEGF-TT than from IO therapies in this setting. Future approaches utilizing radiographic tools and biomarker-based liquid biopsies are warranted to detect occult metastatic disease and identify candidate patients for adjuvant IO therapy. PATIENT SUMMARY: Adjuvant pembrolizumab significantly improved overall survival in renal cell carcinoma (RCC). There are limited data on clinical outcomes after the recurrence of RCC tumors following adjuvant immunotherapy. In this study, we find that patients respond to subsequent systemic therapies across different treatment options.
- MeSH
- adjuvantní chemoterapie MeSH
- doba přežití bez progrese choroby MeSH
- humanizované monoklonální protilátky terapeutické užití škodlivé účinky MeSH
- imunoterapie metody MeSH
- karcinom z renálních buněk * farmakoterapie sekundární mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory ledvin * farmakoterapie patologie mortalita MeSH
- protinádorové látky imunologicky aktivní terapeutické užití škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Léčba 177Lu-PSMA-617 se nově uplatňuje v léčbě metastazujícího kastračně rezistentního karcinomu prostaty po selhání přípravků ARTA a taxanové chemoterapie. Účinnost byla prokázána v klinické studii VISION. V současnosti probíhají klinické studie s 177Lu-PSMA-617 v léčbě karcinomu prostaty i v indikaci hormonálně senzitivního onemocnění a dále také v kombinační léčbě.
Treatment with 177Lu-PSMA-617 is used for the treatment of metastatic castration resistant prostate cancer after the failure of ARPI and taxan based chemotherapy. Efficiency has been proven in a clinical trial VISION. Currently, clinical trials with 177Lu-PSMA-617 are underway in prostate cancer and in the indication of hormone sensitive disease and in combination treatment.
- Klíčová slova
- 177Lu-PSMA-617, studie VISION, studie Therap,
- MeSH
- analýza přežití MeSH
- doba přežití bez progrese choroby MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- lutecium * terapeutické užití MeSH
- membránový potenciál mitochondrií MeSH
- metastázy nádorů farmakoterapie MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie MeSH
- prostatický specifický antigen MeSH
- radiofarmaka * terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
BACKGROUND: Treatment options for metastatic renal cell carcinoma (mRCC) are rapidly expanding, and immunotherapy using checkpoint inhibitors is a first- or second-line option for most patients. OBJECTIVE: The objective of the present retrospective analysis was to explore the real-world impact of checkpoint inhibitor-based immunotherapy compared with therapy using other types of targeted therapies using a large real-world database. METHODS: RenIS, a registry of patients with mRCC was used as a data source. Outcomes were compared for cohorts treated with TKIs or mTOR inhibitors only [targeted therapy (TT) cohort] versus patients who received immunotherapy (IO) using a checkpoint inhibitor in any line of treatment (IO cohort). Data from a total of 1981 patients were extracted from the registry, including 1767 patients in the TT cohort and 214 patients in the IO cohort. RESULTS: The median overall survival from the initiation of first-line treatment was 24.5 months versus not reached (p < 0.001) in the TT cohort versus the IO cohort, respectively [HR 0.23, 95% CI (0.17-0.31), p < 0.001]. The probability of 5-year survival was 24.2 versus 67.9% in the TT cohort versus the IO cohort, respectively. Immunotherapy in any line of treatment was associated with a lower risk of death. Overall survival was superior for patients receiving immunotherapy as the first or second treatment line compared with patients treated with non-immunological targeted therapy. CONCLUSION: In real-world patients with mRCC, immunotherapy is associated with significant survival benefit. The present retrospective analysis shows the real-world benefit of second-line immunotherapy in patients previously treated with tyrosine-kinase inhibitors.
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting. METHODS: We report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal. RESULTS: Currently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term. CONCLUSION: Herein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.
- Publikační typ
- kazuistiky MeSH
Kazuistika je o pacientce s metastazujícím renálním karcinomem s dobrým prognostickým skóre podle klasifikace International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), která byla léčena v první linii kombinací avelumab + axitinib. Léčba byla komplikována nežádoucími účinky (imunitně podmíněná artritida a hepatitida, stomatitida, hand-foot syndrom), ale nakonec bylo dosaženo kompletní remise onemocnění.
The case report is about a patient with metastatic renal cell carcinoma with a good prognostic score according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) who was treated in the first line with a combination of avelumab + axitinib. The treatment was complicated by side effects (immune-related arthritis and hepatitis, stomatitis, hand-foot syndrome), but a complete remission was achieved.
- Klíčová slova
- avelumab,
- MeSH
- axitinib škodlivé účinky terapeutické užití MeSH
- biopsie tenkou jehlou pod endosonografickou kontrolou MeSH
- histologické techniky MeSH
- imunoterapie škodlivé účinky MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití toxicita MeSH
- karcinom z renálních buněk * diagnóza farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- monoklonální protilátky škodlivé účinky terapeutické užití MeSH
- nemoci imunitního systému etiologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND/AIM: Biomarkers that would identify patients unlikely to respond to immunotherapy with immune checkpoint inhibitors (ICIs) remain an unmet medical need. PATIENTS AND METHODS: In the present study, we have retrospectively evaluated the association between biomarkers of immune activation and outcome in metastatic renal cell carcinoma (mRCC) patients treated with ICIs. The laboratory and clinical data of 79 consecutive patients with histologically confirmed mRCC treated with ICI-based immunotherapy have been analyzed. RESULTS: Patients who progressed or died at 4 months had higher prognostic score, higher serum C-reactive protein (CRP) and neopterin, and urinary neopterin, and lower serum albumin and hemoglobin concentration. CONCLUSION: Biomarkers of activation of immune response, in particular serum neopterin/creatinine ratio, are associated with outcome in mRCC patients treated with ICI immunotherapy.
- Publikační typ
- abstrakt z konference MeSH
Sarkomatoidní podtyp karcinomu ledviny se vyskytuje vzácně. Je charakteristický velmi špatnou prognózou a nízkou odpovědí na terapii tyrosinkinázovými inhibitory. Novým standardem léčby se stávají check-point inhibitory (inhibitory kontrolních bodů) v kombinaci ipilimumab + nivolumab. Tato kazuistika představuje pacienta se světlobuněčným karcinomem ledviny se sarkomatoidní dediferenciací, který byl již vstupně generalizovaný a se špatnou prognózou. Pacient byl léčen kombinací ipilimumab + nivolumab s dobrou klinickou odezvou, radiologickou odezvou v podobě stabilizace nemoci a přežitím více než 2 roky.
Sarcomatoid renal cell carcinoma occurs rarely. It is characterized by a very poor prognosis and a low response to treatment with tyrosine kinase inhibitors. Combination of the checkpoint inhibitors ipilimumab and nivolumab is becoming a new standard of treatment. The case report presents a patient with clear-cell renal cell carcinoma with sarcomatoid dedifferentiation that was already generalized at presentation and had a poor prognosis. The patient was treated with the combination of ipilimumab and nivolumab, resulting in a good clinical response, a radiological response in the form of disease stabilization, and a survival of more than two years.
- MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů farmakologie terapeutické užití MeSH
- karcinom z renálních buněk * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory ledvin * farmakoterapie MeSH
- nádory plic farmakoterapie sekundární MeSH
- nivolumab farmakologie terapeutické užití MeSH
- protokoly protinádorové léčby MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
