e21523 Background: Little is known about the outcome of adjuvant therapy in melanoma patients bey... more e21523 Background: Little is known about the outcome of adjuvant therapy in melanoma patients beyond the clinical trial setting. The Dutch Melanoma treatment Registry (DMTR) is a population-based registry, set up in July 2013 to monitor the safety and quality of melanoma care. Since 2019, adjuvant treated melanoma patients have also been registered in the DMTR, following approval and reimbursement of adjuvant treatment in the Netherlands in December 2018. Methods: Analyses were performed on melanoma patients treated with adjuvant anti-PD1 therapy included in the DMTR between 01-07-2018 and 31-12-2019. Descriptive statistics were used to analyze patient-, and treatment characteristics, and death as well as relapse rates. Results: Six hundred and fifty-seven patients treated with adjuvant systemic therapy were included in the DMTR. The majority (94%) of these patients was treated with anti-PD1. Twenty percent of the anti-PD1-treated patients developed grade ā„3 toxicity. Of the 279 pat...
e21527 Background: Recent data in Japanese patients suggest poor outcomes for anti-PD1 in acral m... more e21527 Background: Recent data in Japanese patients suggest poor outcomes for anti-PD1 in acral melanoma (AM), with no data available on combination treatment. The objective of this study was to analyze the efficacy of anti-PD1 monotherapy and anti-PD1 and anti-CTLA4 combination therapy in these patients. Methods: Our study population consisted of patients registered in the nationwide prospective Dutch Melanoma Treatment Registry between 2014 and 2020. We calculated objective response rate (ORR) in all unresectable stage III and IV AM and nonacral cutaneous melanoma (NAM) patients treated with anti-PD1, and combination anti-PD1 and anti-CTLA4. Progression-free survival (PFS), and overall survival (OS) were estimated for first-line treated patients. A Cox proportional hazard analysis was performed to adjust for potential confounders. Results: Nighty-five AM patients received at least one dose of anti-PD1 monotherapy, of whom 58 (61%) as first-line treatment. ORR was 28% (complete res...
9558 Background: The ability to analyze tumor mutation profiles has altered the oncology treatmen... more 9558 Background: The ability to analyze tumor mutation profiles has altered the oncology treatment landscape over the past decades. However, little is known about the effect of specific gene mutations on the response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: All unresectable stage IIIc and IV patients with BRAF V600, NRAS mutations and BRAF and NRAS wild-type patients treated with anti-PD-1 or ipilimumab-nivolumab between 2012 and 2020 were included from the Dutch Melanoma Treatment Registry, a nationwide population-based registry. Outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A Cox model was used to analyze the association of possible prognostic factors with PFS and OS. Results: In total 1358 first-line patients treated with anti-PD-1 and 524 treated with ipilimumab-nivolumab were included. Median follow-up was 25.6 months for anti-PD-1 treated patients and 16.3 months for ipilimuma...
9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastati... more 9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ā„65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ā„3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ā„3 toxicity did n...
Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), a... more Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), and it is unclear whether these patients benefit equally from novel therapies. In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and/or targeted therapy. OS was estimated using the KaplanāMeier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnos...
Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hosp... more Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands. Methods: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centersā performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared. Results: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new system...
Background: Previous trials suggest no differences in immunotherapy treatment between older and y... more Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of āreal-worldā older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ā„65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ā„3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ā„75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65ā75 and ā„7...
Background The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab an... more Background The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response. Methods The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a co...
tested ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose IFN-a (HDI) and S1404 (NĀ¼1... more tested ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose IFN-a (HDI) and S1404 (NĀ¼1207) that tested pembrolizumab versus patient/physician choice of ipi10 or HDI. We sought to estimate the incidence of GSL as reported by trial investigators in the combined datasets utilizing descriptive statistics as summarized in the table, along with the corresponding CTCAE grades. Results: Among 2878 patients treated with ICIs or with HDI in E1609 and S1404, 523 were treated with ipi3, 932 with ipi10, 640 with pembrolizumab and 783 with HDI. A total of 11 GSL cases were reported. Cases were reported with ipi10, followed by pembrolizumab, ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Conclusions: Granulomatous and sarcoid-like lesions (GSL) following adjuvant anti-CTLA4 and anti-PD1 antibody therapy in high-risk melanoma were reported rarely. Reported cases ranged in grade from 1-3 and appeared manageable. Careful attention to these events and their reporting would be essential to better guide practice and management guidelines.
For patients with newly diagnosed metastatic melanoma, rapid BRAF mutation (mBRAF) assessment is ... more For patients with newly diagnosed metastatic melanoma, rapid BRAF mutation (mBRAF) assessment is vital to promptly initiate systemic therapy. Additionally, blood-based biomarkers are desired to monitor and predict treatment response. Circulating tumor DNA (ctDNA) has shown great promise for minimally invasive mBRAF assessment and treatment monitoring, but validation studies are needed. This prospective study utilized longitudinal plasma samples at regular timepoints (0, 6, 12, 18 weeks) to address the clinical validity of ctDNA measurements in stage IV melanoma patients with elevated serum lactate dehydrogenase (LDH > 250U/L) starting first-line systemic treatment. Using droplet digital PCR, the plasma mBRAF abundance was assessed in 53 patients with a BRAFV600 tissue mutation. Plasma mBRAF was detected in 50/51 patients at baseline (98% sensitivity; median fraction abundance of 19.5%) and 0/17 controls (100% specificity). Patients in whom plasma mBRAF became undetectable during ...
e15596 Background: Diarrhea is a frequently occurring adverse event of treatment with vascular en... more e15596 Background: Diarrhea is a frequently occurring adverse event of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). It impairs quality of life and leads to dose reductions and treatment interruptions. The aim of this pilot study is to gain insight in the underlying pathophysiologal mechanism of diarrhea in patients treated with VEGFR TKIs. Methods: We included ten patients with metastatic renal cell carcinoma who were treated with a VEGFR TKI and developed diarrhea. Blood, feces and urine samples were extensively analyzed and all patients underwent endoscopy with biopsies of the upper and lower gastro-intestinal (GI) tract. Results: Besides the diarrhea, patients complained of pyrosis (n = 6) and abdominal cramps (n = 5). While decreased plasma concentrations of vitamins D and B12 were found in 6 and 7 patients, respectively, all other mineral and electrolyte levels were normal. Sigmoidoscopy was macroscopically normal in the majority of patients and ...
e14014 Background: Despite recent advances in treatment of metastatic clear cell renal cell carci... more e14014 Background: Despite recent advances in treatment of metastatic clear cell renal cell carcinoma (ccRCC), the search for alternative treatment modalities, which can induce durable responses wi...
Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on ... more Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on quality of life. We conducted a randomized phase II trial to assess the palliative value of cediranib, an oral vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or thoracentesis (on day 0), patients with symptomatic malignant ascites and/or pleural effusion were randomized between immediate treatment with cediranib (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on day 29, or after a new puncture was needed. The primary objective of the study was the puncture-free survival, defined as the time from study start (day 1) to the first need for paracentesis or thoracentesis, or time to death, whichever event occurred first. Twelve patients were enrolled. The median puncture-free survival was 45 days (range 10-368) in the Immediate Cediranib patients and 7 days (range 4-13) in the Delayed Cediranib patients (Pā=...
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
Vaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens... more Vaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens is currently being tested as an adjuvant treatment modality for resected locoregional metastatic (stage III) melanoma. Based on its mechanism of action, DC vaccination might potentiate the clinical efficacy of concurrent or sequential immune checkpoint inhibition (ICI). The purpose of this study was to determine the efficacy of ICI administered following recurrent disease during, or after, adjuvant DC vaccination. To this end, we retrospectively analyzed clinical responses of 51 melanoma patients with either irresectable stage III or stage IV disease treated with first-or second-line ICI following recurrence on adjuvant DC vaccination. Patients were analyzed according to the form of ICI administered: PD-1 inhibition monotherapy (nivolumab or pembrolizumab), ipilimumab monotherapy or combined treatment with ipilimumab and nivolumab. Treatment with first-or second-line PD-1 inhibition monotherapy after recurrence on adjuvant DC vaccination resulted in a response rate of 52%. In patients treated with ipilimumab monotherapy and ipilimumab-nivolumab response rates were 35% and 75%, respectively. In conclusion, ICI is effective in melanoma patients with recurrent disease on adjuvant DC vaccination.
e21502 Background: The COVID-19 pandemic COVID had a severe impact on medical care in The Netherl... more e21502 Background: The COVID-19 pandemic COVID had a severe impact on medical care in The Netherlands. So far, few studies have investigated the influence of COVID-19 on advanced melanoma care nationwide. This study aims to investigate the impact of COVID-19 on the systemic treatment of unresectable stage III and IV advanced melanoma patients in the Netherlands. Methods: Data were obtained from the Dutch Melanoma Treatment Registry (DMTR), a population-based nationwide registry of all stage III and IV melanoma patients amenable for systemic treatment. We compared two patient groups dependent on the date of the first diagnosis of metastasis: during the first COVID-19 wave (March 15th 2020 until May 22nd 2020), and a control group during the same period one year earlier. Furthermore, we divided patients into three geographical regions within the Netherlands (north, middle and south). These regions were based on the maximum number of hospital admissions for COVID-19 patients during the...
e21523 Background: Little is known about the outcome of adjuvant therapy in melanoma patients bey... more e21523 Background: Little is known about the outcome of adjuvant therapy in melanoma patients beyond the clinical trial setting. The Dutch Melanoma treatment Registry (DMTR) is a population-based registry, set up in July 2013 to monitor the safety and quality of melanoma care. Since 2019, adjuvant treated melanoma patients have also been registered in the DMTR, following approval and reimbursement of adjuvant treatment in the Netherlands in December 2018. Methods: Analyses were performed on melanoma patients treated with adjuvant anti-PD1 therapy included in the DMTR between 01-07-2018 and 31-12-2019. Descriptive statistics were used to analyze patient-, and treatment characteristics, and death as well as relapse rates. Results: Six hundred and fifty-seven patients treated with adjuvant systemic therapy were included in the DMTR. The majority (94%) of these patients was treated with anti-PD1. Twenty percent of the anti-PD1-treated patients developed grade ā„3 toxicity. Of the 279 pat...
e21527 Background: Recent data in Japanese patients suggest poor outcomes for anti-PD1 in acral m... more e21527 Background: Recent data in Japanese patients suggest poor outcomes for anti-PD1 in acral melanoma (AM), with no data available on combination treatment. The objective of this study was to analyze the efficacy of anti-PD1 monotherapy and anti-PD1 and anti-CTLA4 combination therapy in these patients. Methods: Our study population consisted of patients registered in the nationwide prospective Dutch Melanoma Treatment Registry between 2014 and 2020. We calculated objective response rate (ORR) in all unresectable stage III and IV AM and nonacral cutaneous melanoma (NAM) patients treated with anti-PD1, and combination anti-PD1 and anti-CTLA4. Progression-free survival (PFS), and overall survival (OS) were estimated for first-line treated patients. A Cox proportional hazard analysis was performed to adjust for potential confounders. Results: Nighty-five AM patients received at least one dose of anti-PD1 monotherapy, of whom 58 (61%) as first-line treatment. ORR was 28% (complete res...
9558 Background: The ability to analyze tumor mutation profiles has altered the oncology treatmen... more 9558 Background: The ability to analyze tumor mutation profiles has altered the oncology treatment landscape over the past decades. However, little is known about the effect of specific gene mutations on the response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: All unresectable stage IIIc and IV patients with BRAF V600, NRAS mutations and BRAF and NRAS wild-type patients treated with anti-PD-1 or ipilimumab-nivolumab between 2012 and 2020 were included from the Dutch Melanoma Treatment Registry, a nationwide population-based registry. Outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A Cox model was used to analyze the association of possible prognostic factors with PFS and OS. Results: In total 1358 first-line patients treated with anti-PD-1 and 524 treated with ipilimumab-nivolumab were included. Median follow-up was 25.6 months for anti-PD-1 treated patients and 16.3 months for ipilimuma...
9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastati... more 9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ā„65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ā„3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ā„3 toxicity did n...
Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), a... more Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), and it is unclear whether these patients benefit equally from novel therapies. In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and/or targeted therapy. OS was estimated using the KaplanāMeier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnos...
Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hosp... more Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands. Methods: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centersā performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared. Results: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new system...
Background: Previous trials suggest no differences in immunotherapy treatment between older and y... more Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of āreal-worldā older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ā„65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ā„3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ā„75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65ā75 and ā„7...
Background The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab an... more Background The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response. Methods The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a co...
tested ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose IFN-a (HDI) and S1404 (NĀ¼1... more tested ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose IFN-a (HDI) and S1404 (NĀ¼1207) that tested pembrolizumab versus patient/physician choice of ipi10 or HDI. We sought to estimate the incidence of GSL as reported by trial investigators in the combined datasets utilizing descriptive statistics as summarized in the table, along with the corresponding CTCAE grades. Results: Among 2878 patients treated with ICIs or with HDI in E1609 and S1404, 523 were treated with ipi3, 932 with ipi10, 640 with pembrolizumab and 783 with HDI. A total of 11 GSL cases were reported. Cases were reported with ipi10, followed by pembrolizumab, ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Conclusions: Granulomatous and sarcoid-like lesions (GSL) following adjuvant anti-CTLA4 and anti-PD1 antibody therapy in high-risk melanoma were reported rarely. Reported cases ranged in grade from 1-3 and appeared manageable. Careful attention to these events and their reporting would be essential to better guide practice and management guidelines.
For patients with newly diagnosed metastatic melanoma, rapid BRAF mutation (mBRAF) assessment is ... more For patients with newly diagnosed metastatic melanoma, rapid BRAF mutation (mBRAF) assessment is vital to promptly initiate systemic therapy. Additionally, blood-based biomarkers are desired to monitor and predict treatment response. Circulating tumor DNA (ctDNA) has shown great promise for minimally invasive mBRAF assessment and treatment monitoring, but validation studies are needed. This prospective study utilized longitudinal plasma samples at regular timepoints (0, 6, 12, 18 weeks) to address the clinical validity of ctDNA measurements in stage IV melanoma patients with elevated serum lactate dehydrogenase (LDH > 250U/L) starting first-line systemic treatment. Using droplet digital PCR, the plasma mBRAF abundance was assessed in 53 patients with a BRAFV600 tissue mutation. Plasma mBRAF was detected in 50/51 patients at baseline (98% sensitivity; median fraction abundance of 19.5%) and 0/17 controls (100% specificity). Patients in whom plasma mBRAF became undetectable during ...
e15596 Background: Diarrhea is a frequently occurring adverse event of treatment with vascular en... more e15596 Background: Diarrhea is a frequently occurring adverse event of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). It impairs quality of life and leads to dose reductions and treatment interruptions. The aim of this pilot study is to gain insight in the underlying pathophysiologal mechanism of diarrhea in patients treated with VEGFR TKIs. Methods: We included ten patients with metastatic renal cell carcinoma who were treated with a VEGFR TKI and developed diarrhea. Blood, feces and urine samples were extensively analyzed and all patients underwent endoscopy with biopsies of the upper and lower gastro-intestinal (GI) tract. Results: Besides the diarrhea, patients complained of pyrosis (n = 6) and abdominal cramps (n = 5). While decreased plasma concentrations of vitamins D and B12 were found in 6 and 7 patients, respectively, all other mineral and electrolyte levels were normal. Sigmoidoscopy was macroscopically normal in the majority of patients and ...
e14014 Background: Despite recent advances in treatment of metastatic clear cell renal cell carci... more e14014 Background: Despite recent advances in treatment of metastatic clear cell renal cell carcinoma (ccRCC), the search for alternative treatment modalities, which can induce durable responses wi...
Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on ... more Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on quality of life. We conducted a randomized phase II trial to assess the palliative value of cediranib, an oral vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or thoracentesis (on day 0), patients with symptomatic malignant ascites and/or pleural effusion were randomized between immediate treatment with cediranib (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on day 29, or after a new puncture was needed. The primary objective of the study was the puncture-free survival, defined as the time from study start (day 1) to the first need for paracentesis or thoracentesis, or time to death, whichever event occurred first. Twelve patients were enrolled. The median puncture-free survival was 45 days (range 10-368) in the Immediate Cediranib patients and 7 days (range 4-13) in the Delayed Cediranib patients (Pā=...
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
Vaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens... more Vaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens is currently being tested as an adjuvant treatment modality for resected locoregional metastatic (stage III) melanoma. Based on its mechanism of action, DC vaccination might potentiate the clinical efficacy of concurrent or sequential immune checkpoint inhibition (ICI). The purpose of this study was to determine the efficacy of ICI administered following recurrent disease during, or after, adjuvant DC vaccination. To this end, we retrospectively analyzed clinical responses of 51 melanoma patients with either irresectable stage III or stage IV disease treated with first-or second-line ICI following recurrence on adjuvant DC vaccination. Patients were analyzed according to the form of ICI administered: PD-1 inhibition monotherapy (nivolumab or pembrolizumab), ipilimumab monotherapy or combined treatment with ipilimumab and nivolumab. Treatment with first-or second-line PD-1 inhibition monotherapy after recurrence on adjuvant DC vaccination resulted in a response rate of 52%. In patients treated with ipilimumab monotherapy and ipilimumab-nivolumab response rates were 35% and 75%, respectively. In conclusion, ICI is effective in melanoma patients with recurrent disease on adjuvant DC vaccination.
e21502 Background: The COVID-19 pandemic COVID had a severe impact on medical care in The Netherl... more e21502 Background: The COVID-19 pandemic COVID had a severe impact on medical care in The Netherlands. So far, few studies have investigated the influence of COVID-19 on advanced melanoma care nationwide. This study aims to investigate the impact of COVID-19 on the systemic treatment of unresectable stage III and IV advanced melanoma patients in the Netherlands. Methods: Data were obtained from the Dutch Melanoma Treatment Registry (DMTR), a population-based nationwide registry of all stage III and IV melanoma patients amenable for systemic treatment. We compared two patient groups dependent on the date of the first diagnosis of metastasis: during the first COVID-19 wave (March 15th 2020 until May 22nd 2020), and a control group during the same period one year earlier. Furthermore, we divided patients into three geographical regions within the Netherlands (north, middle and south). These regions were based on the maximum number of hospital admissions for COVID-19 patients during the...
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