12 results on '"van den Eertwegh, Alfons J. M."'
Search Results
2. Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands
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van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, van den Eertwegh, Alfons J M, Internal medicine, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Medical oncology, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Medical Oncology, and Radiology & Nuclear Medicine
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Pharmacology ,Cancer Research ,Ipilimumab plus nivolumab ,Antineoplastic Combined Chemotherapy Protocols/adverse effects ,Immunology ,real world ,Brain Neoplasms/drug therapy ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,population-based ,Nivolumab/therapeutic use ,POOLED ANALYSIS ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,Melanoma/pathology ,SURVIVAL ,Immunology and Allergy ,Humans ,METASTATIC MELANOMA ,immunotherapy ,Ipilimumab/therapeutic use ,Netherlands - Abstract
Item does not contain fulltext In phase III trials, ipilimumab plus nivolumab combination therapy is highly efficacious for advanced melanoma, despite many treatment-related grades 3-4 adverse events. Here, we report real-world safety and survival outcomes of ipilimumab plus nivolumab for advanced melanoma. Patients with advanced melanoma who received first-line ipilimumab plus nivolumab between January 1, 2015 and June 30, 2021 were selected from the Dutch Melanoma Treatment Registry. We evaluated response status at 3, 6, 12, 18, and 24 months. OS and PFS were estimated with the Kaplan-Meier method. Separate analyses were performed for patients with or without brain metastases and for patients who met the inclusion criteria of the Checkmate-067 trial. In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 adverse events, with 211 of the (58.6%) patients requiring hospital admission. The median treatment duration was 42 days (IQR = 31-139). At 24 months, disease control was achieved in 37% of patients. Median PFS since the start of treatment was 6.6 months (95% CI: 5.3-8.7), and median OS was 28.7 months (95% CI: 20.7-42.2). CheckMate-067 trial-like patients had a 4-year OS of 50% (95% CI: 43-59). Among patients with no asymptomatic or symptomatic brain metastases, the 4-year OS probabilities were 48% (95% CI: 41-55), 45% (95% CI: 35-57), and 32% (95% CI: 23-46). Ipilimumab plus nivolumab can achieve long-term survival in advanced melanoma patients in a real-world setting, including patients not represented in the CheckMate-067 trial. However, the proportion of patients with disease control in the real world is lower compared with clinical trials.
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- 2023
3. Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status
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MS Medische Oncologie, Infection & Immunity, Cancer, Pathologie Pathologen staf, van Breeschoten, Jesper, Wouters, Michel W J M, de Wreede, Liesbeth C, Hilarius, Doranne H, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers, Marye J, van den Eertwegh, Alfons J M, MS Medische Oncologie, Infection & Immunity, Cancer, Pathologie Pathologen staf, van Breeschoten, Jesper, Wouters, Michel W J M, de Wreede, Liesbeth C, Hilarius, Doranne H, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers, Marye J, and van den Eertwegh, Alfons J M
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- 2021
4. Vemurafenib in BRAF-mutant metastatic melanoma patients in real-world clinical practice: prognostic factors associated with clinical outcomes.
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Schouwenburg, Maartje G., Jochems, Anouk, Leeneman, Brenda, Franken, Margreet G., van den Eertwegh, Alfons J. M., Haanen, John B. A. G., van Zeijl, Michiel C. T., Aarts, Maureen J., van Akkooi, Alexander C. J., van den Berkmortel, Franchette W. P. J., Blokx, Willeke A. M., de Groot, Jan Willem B., Hospers, Geke A. P., Kapiteijn, Ellen, Koornstra, Rutger H., Kruit, Wim H., Louwman, Marieke W. J., Piersma, Djura, van Rijn, Rozemarijn S., and Suijkerbuijk, Karijn P. M.
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- 2018
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5. A Phase 1 Trial of Cabazitaxel Combined With 188Re-Hydroxyethylidene Diphosphonate in Patients With Metastatic Castration-Resistant Prostate Cancer Who Progressed on or After a Docetaxel-Containing Treatment: The ReCab Trial.
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van Dodewaard-de Jong, Joyce M., Bouman-Wammes, Esther W., Bloemendal, Haiko J., Verheul, Henk M. W., de Klerk, John M. H., and van den Eertwegh, Alfons J. M.
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- 2017
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6. Recent developments and future challenges in immune checkpoint inhibitory cancer treatment.
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Koster, Bas D., de Gruijl, Tanja D., and van den Eertwegh, Alfons J. M.
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- 2015
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7. Clinical/Scientific Notes.
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Killestein, Joep, Leurs, Cyra E., Hoogervorst, Erwin L. J., van Eijk, Jeroen, Mostert, Jop P., van den Eertwegh, Alfons J. M., and Uitdehaag, Bernard M. J.
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- 2017
8. Five cases of malignant melanoma during fingolimod treatment in Dutch patients with MS.
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Killestein, Joep, Leurs, Cyra E, Hoogervorst, Erwin L J, van Eijk, Jeroen, Mostert, Jop P, van den Eertwegh, Alfons J M, and Uitdehaag, Bernard M J
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- 2017
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9. Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status.
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van Breeschoten J, Wouters MWJM, de Wreede LC, Hilarius DH, Haanen JB, Blank CU, Aarts MJB, van den Berkmortel FWPJ, de Groot JB, Hospers GAP, Kapiteijn E, Piersma D, van Rijn RS, Suijkerbuijk KPM, Blokx WAM, Ten Tije AJ, van der Veldt AAM, Vreugdenhil G, Boers MJ, and van den Eertwegh AJM
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- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, B7-H1 Antigen antagonists & inhibitors, Brain Neoplasms secondary, Female, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Melanoma therapy, Netherlands, Proportional Hazards Models, Survival Rate, Melanoma genetics, Melanoma mortality, Mutation, Proto-Oncogene Proteins B-raf genetics
- Abstract
Objective: The aim of this study was to evaluate treatment patterns and overall survival (OS) of patients with BRAFV600 wild-type and BRAFV600-mutant advanced melanoma in the Netherlands., Methods: We selected patients of 18 years and over, diagnosed between 2016 and 2017 with unresectable stage IIIC or IV melanoma, registered in the Dutch Melanoma Treatment Registry. To assess the association of BRAFV600-mutation status with OS we used the Cox proportional-hazards model., Results: A total of 642 BRAFV600 wild-type and 853 mutant patients were included in the analysis. Median OS did not differ significantly between both groups, 15.2 months (95% confidence interval [CI]: 13.2-19.2) versus 20.6 months (95% CI: 18.3-25.0). Survival rates at 6 and 12 months were significantly lower for BRAFV600 wild-type patients compared with BRAFV600-mutant patients, 72.0% (95% CI: 68.6-75.6) and 56.0% (95% CI: 52.2-60.0) versus 83.4% (95% CI: 80.9-85.9) and 65.7% (95% CI: 62.6-69.0). Two-year survival was not significantly different between both groups, 41.1% (95% CI: 37.2-45.3) versus 47.0% (95% CI: 43.6-60.6). Between 0 and 10 months, BRAFV600 wild-type patients had a decreased survival with a hazard ratio for OS of 2.00 (95% CI: 1.62-2.46) but this effect disappeared after 10 months. At 12 months, BRAFV600-mutant patients had started with second-line systemic treatment more often compared with BRAFV600 wild-type patients (50% vs. 19%)., Conclusion: These results suggest that advanced BRAFV600 wild-type melanoma patients have worse survival than BRAFV600-mutated patients during the first 10 months after diagnosis because of less available treatment options., Competing Interests: J.B.H. has advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics and has received research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, Neon Therapeutics. All grants were paid to the institutions. C.U.B. has advisory relationships with, Bristol-Myers Squibb, Genmab, GSK, Lilly, MSD, Roche, Novartis, Pfizer and grant support by BMS, Novartis, and NanoString. J.-W.B.d.G. has received personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre Fabre, Servier, MSD, Novartis. G.A.P.H. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, BMS. She received honoraria from Novartis, Pierre Fabre, and Roche and has received research grants not related to this paper from Bristol-Myers Squibb, Seerave. A.A.M.v.d.V. has consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai. E.K. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck, Pierre Fabre, EISAI, Bayer, Genzyme-Sanofi and received research grants not related to this paper from Novartis and Bristol-Myers Squibb. K.P.M.S. has consulting/advisory relationships with BMS and MSD. She received honoraria from Novartis, Pierre Fabre, and Roche. A.J.M.v.d.E. has consulting/advisory relationships with BMS, Roche, MSD, and Novartis. He received a study grant from Roche. The funders had no role in the writing of this article or decision to submit it for publication. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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10. Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study.
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van Zeijl MCT, Haanen JBAG, Wouters MWJM, de Wreede LC, Jochems A, Aarts MJB, van den Berkmortel FWPJ, de Groot JWB, Hospers GAP, Kapiteijn EW, Piersma D, van Rijn RS, Suijkerbuijk KPM, Ten Tije AJ, van der Veldt AAM, Vreugdenhil G, van der Hoeven KJM, and van den Eertwegh AJM
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- Aged, Aged, 80 and over, Disease Management, Female, Health Care Surveys, Humans, Immune Checkpoint Inhibitors administration & dosage, Immune Checkpoint Inhibitors adverse effects, Male, Melanoma pathology, Middle Aged, Molecular Targeted Therapy, Neoplasm Staging, Netherlands epidemiology, Prognosis, Treatment Outcome, Immune Checkpoint Inhibitors therapeutic use, Melanoma drug therapy, Melanoma epidemiology, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
The efficacy of anti-programmed death-1 (PD-1) monotherapy for advanced melanoma has been established, but it is unknown to what extent patients benefit in the real world. In this observational study with nationwide population-based data from the Dutch Melanoma Treatment Registry, we analyzed real-world outcomes of first-line anti-PD-1 monotherapy in advanced melanoma patients diagnosed in 2015 to 2016. Overall survival (OS) was estimated with the Kaplan-Meier method. Competing risks analysis was used to estimate probabilities for second-line treatment, with death as competing risk. With a Cox model, the association of factors with OS was estimated. Patients who received anti-PD-1 monotherapy (n=550) had a median age of 65 years and 502 (95%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, 383 (70%) had normal lactate dehydrogenase (LDH), 370 (67%) had stage IV-M1c disease, and in 441 (81%), brain metastases were absent. The median OS was 24 months [95% confidence interval (CI): 20-30 mo]. The median OS of patients normally eligible for phase III trial participation was 31 months (95% CI: 23-not estimable). The BRAF mutation was associated with superior OS. ECOG PS of ≥1, symptomatic brain metastases, and liver metastases were associated with inferior OS and, together with elevated LDH, with death before second-line treatment. Patients with a complete response had a 2-year OS probability from first reported complete response of 92% (95% CI: 86%-99%). Real-world advanced melanoma patients in the Netherlands have benefitted from anti-PD-1 monotherapy. ECOG PS ≥1, symptomatic brain metastasis, liver metastasis, and elevated LDH are important prognostic factors for survival. The additional information that this study provides could help to improve more effective use in the real world.
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- 2020
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11. Selective transduction of dendritic cells in human lymph nodes and superior induction of high-avidity melanoma-reactive cytotoxic T cells by a CD40-targeted adenovirus.
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Hangalapura BN, Oosterhoff D, Aggarwal S, Wijnands PG, van de Ven R, Santegoets SJ, van den Tol MP, Hooijberg E, Pereboev A, van den Eertwegh AJ, Curiel DT, Scheper RJ, and de Gruijl TD
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- CD4 Antigens biosynthesis, CD40 Ligand genetics, CD40 Ligand immunology, CD40 Ligand metabolism, Cytotoxicity, Immunologic, Dendritic Cells immunology, Dendritic Cells pathology, Forkhead Transcription Factors biosynthesis, Humans, Interferon-gamma metabolism, Interleukin-2 Receptor alpha Subunit biosynthesis, K562 Cells, Lymph Nodes pathology, MART-1 Antigen genetics, MART-1 Antigen immunology, MART-1 Antigen metabolism, Melanoma immunology, Protein Engineering, Recombinant Fusion Proteins genetics, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic pathology, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, T-Lymphocytes, Regulatory pathology, Transduction, Genetic, Adenoviridae genetics, CD40 Antigens metabolism, Dendritic Cells metabolism, Immunotherapy, Melanoma therapy, T-Lymphocytes, Cytotoxic metabolism
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Targeted delivery of tumor antigen genes to dendritic cells (DCs) using adenoviral (Ad) vectors holds great potential for cancer immunotherapy. We previously showed that CD40 targeting of Ad vectors enhanced specific transduction of DC in human skin, while simultaneously ensuring their stable maturation and superior allogeneic T-cell stimulatory capacity. In this study, we evaluated whether CD40-targeted Ad encoding the full-length melanoma antigen recognized by T cells-1 (CD40-Ad-MART-1) could be used to efficiently and selectively transduce conventional and plasmacytoid DC to prime melanoma-specific CD8(+) T-effector cells in human melanoma-draining sentinel lymph nodes (SLNs). CD40 targeting of Ad was achieved using a bispecific fusion protein, binding and neutralizing the Ad fiber knob through soluble coxsackie and adenovirus receptor while retargeting the virus to hCD40 through the tumor necrosis factor-like domain of mCD40L. Selective transduction of conventional and plasmacytoid DC subsets by CD40-Ad was observed in suspensions of human melanoma-draining SLN. Moreover, CD40-Ad-MART-1 enhanced the expansion of functional MART-1-specific CD8(+) T cells from SLN with concomitant decreases in CD4:CD8 T-cell ratios and CD4(+)CD25(hi)FoxP3(+) regulatory T-cell rates. Additional studies revealed that transduction and activation of monocyte-derived DCs with CD40-Ad-MART-1 significantly enhanced their priming efficiency of functional CD8(+) effector T cells with high avidity. These findings provide preclinical evidence of possible efficacy of this approach for cancer immunotherapy.
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- 2010
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12. Reduction in skin microvascular density and changes in vessel morphology in patients treated with sunitinib.
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van der Veldt AA, de Boer MP, Boven E, Eringa EC, van den Eertwegh AJ, van Hinsbergh VW, Smulders YM, and Serné EH
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- Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors therapeutic use, Capillaries anatomy & histology, Capillaries physiopathology, Female, Humans, Hypertension chemically induced, Indoles therapeutic use, Kidney Neoplasms drug therapy, Male, Middle Aged, Pyrroles therapeutic use, Skin drug effects, Skin physiopathology, Sunitinib, Angiogenesis Inhibitors adverse effects, Capillaries drug effects, Indoles adverse effects, Pyrroles adverse effects, Skin blood supply
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Hypertension is a common side effect in cancer patients treated with inhibitors of vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling and may represent a marker of clinical benefit. Functional rarefaction (a decrease in perfused microvessels) or structural rarefaction (a reduction in anatomic capillary density) may play an important role in the development of hypertension. We investigated whether sunitinib caused impairment of microvascular function and/or reduction of capillary density in patients with metastatic renal cell cancer (mRCC). Sixteen mRCC patients were treated with sunitinib (50 mg/day). Assessments of 24-h ambulatory blood pressure, microvascular endothelial function by laser Doppler fluxmetry, and capillary density by capillary microscopy were performed at baseline and days 14 and 28. Median blood pressure had increased on day 14 (systolic 10 mmHg, P<0.01 and diastolic blood pressure 8 mmHg, P<0.01). Capillary density had decreased from 69 to 61 capillaries/mm (P<0.01). This decrease was related to the increase in systolic and diastolic blood pressure (r=-0.57, P<0.05 and r=-0.68, P<0.01, respectively). A more pronounced decrease in capillary density was associated with increased visibility of the subpapillary plexus (P=0.041). Preliminary findings indicated that median progression-free survival was significantly prolonged in patients with a greater than 6 capillaries/mm decrease in density as compared with patients with a less pronounced decrease (P=0.044). In conclusion, reduction in skin capillary density is associated with a rise in blood pressure during sunitinib therapy and, by itself, might be useful as a predictive marker of clinical outcome.
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- 2010
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