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1. Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Blankenstein, Stephanie A., Bonenkamp, Johannes J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Blokx, Willeke A. M., Boers-Sonderen, Marye J., van den Eertwegh, Alfons J. M., Franken, Margreet G., de Groot, Jan Willem B., Haanen, John B. A. G., Hospers, Geke A. P., Kapiteijn, Ellen W., van Not, Olivier J., Piersma, Djura, van Rijn, Rozemarijn S., Suijkerbuijk, Karijn P. M., van der Veldt, Astrid A. M., Vreugdenhil, Gerard, Westgeest, Hans M., Wouters, Michel W. J. M., and van Akkooi, Alexander C. J.

Published
2023
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2. Adjuvant treatment with anti‐PD‐1 in acral melanoma: A nationwide study.

Author

Bloem, Manja, van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Blokx, Willeke A. M., Boers‐Sonderen, Marye J., Bonenkamp, Johannes J., de Groot, Jan‐Willem B., Haanen, John B., Hospers, Geke A. P., Kapiteijn, Ellen W., de Meza, Melissa M., Piersma, Djura, van Rijn, Rozemarijn S., Stevense‐den Boer, Marion A. M., van der Veldt, Astrid A. M., Vreugdenhil, Gerard, van den Eertwegh, Alfons J. M., and Suijkerbuijk, Karijn P. M.

Subjects
IMMUNE checkpoint inhibitors, IMMUNOLOGICAL adjuvants, OVERALL survival, REGRESSION analysis, MELANOMA
Abstract

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti‐PD‐1 after complete resection. All stages III–IV AM and CM patients receiving adjuvant anti‐PD‐1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence‐free survival (RFS), distant metastasis‐free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5–29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p =.002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07–2.17; p =.019). Two‐year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p =.050). Two‐year OS was significantly lower in AM (71.5% vs. 84.3%; p =.027). The results of this study suggest a poorer outcome of adjuvant‐treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high‐risk AM. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Author

Affandi, Alsya J., Grabowska, Joanna, Olesek, Katarzyna, Venegas, Miguel Lopez, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P. G., Pijffers, Helen J., Ambrosini, Martino, Kalay, Hakan, O’Toole, Tom, Zwart, Eline S., Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J., Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M. M.

Published
2020

5. ASO Visual Abstract: Is a History of Optimal Staging by SLNB in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Blankenstein, Stephanie A., Bonenkamp, Johannes J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Blokx, Willeke A. M., Boers-Sonderen, Marye J., van den Eertwegh, Alfons J. M., Franken, Margreet G., de Groot, Jan Willem B., Haanen, John B. A. G., Hospers, Geke A. P., Kapiteijn, Ellen W., van Not, Olivier J., Piersma, Djura, van Rijn, Rozemarijn S., Suijkerbuijk, Karijn P. M., van der Veldt, Astrid A. M., Vreugdenhil, Gerard, Westgeest, Hans M., Wouters, Michel W. J. M., and van Akkooi, Alexander C. J.

Published
2023
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6. Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

Author

MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, van den Eertwegh, Alfons J M, MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, and van den Eertwegh, Alfons J M

Published
2024

7. The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Author

MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, and Haanen, John B A G

Published
2024

8. BRAF/MEK inhibitor rechallenge in advanced melanoma patients

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, and Suijkerbuijk, Karijn P M

Published
2024

9. Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2024

10. Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

Author

Gogas, Helen, Ravimohan, Shruthi, Datta, Antara, Chhibber, Aparna, Couselo, Eva Muñoz, Diab, Adi, Pereira, Caio, Quéreux, Gaëlle, Sandhu, Shahneen, Curti, Brendan, Khushalani, Nikhil I., Taylor, Matthew H., Daniels, Gregory A., Spreafico, Anna, Meniawy, Tarek, Van Den Eertwegh, Alfons J. M., Sun, Yongliang, Arriaga, Yull, Zhou, Ming, and Long, Georgina V.

Subjects
REGULATORY T cells, TUMOR markers, NIVOLUMAB, BIOMARKERS, T cells
Abstract

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma.

Author

Leek, Lindsay V. M., Notohardjo, Jessica C. L., de Joode, Karlijn, Velker, Eline L., Haanen, John B. A. G., Suijkerbuijk, Karijn P. M., Aarts, Maureen J. B., de Groot, Jan Willem B., Kapiteijn, Ellen, van den Berkmortel, Franchette W. P. J., Westgeest, Hans M., de Gruijl, Tanja D., Retel, Valesca P., Cuppen, Edwin, van der Veldt, Astrid A. M., Labots, Mariette, Voest, Emile E., van de Haar, Joris, and van den Eertwegh, Alfons J. M.

Subjects
MELANOMA, PROGRAMMED cell death 1 receptors, LIVER metastasis, BIOMARKERS, METASTASIS, PROGRESSION-free survival
Abstract

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10–7.67, Cox P = 2.63e−05) and PFS (HR = 3.72, 95% CI 2.06–6.73, Cox P = 1.38e−05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24–6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16–3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2–3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08–3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH. [ABSTRACT FROM AUTHOR]

Published
2024
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12. BRAF/MEK inhibitor rechallenge in advanced melanoma patients.

Author

Van Not, Olivier J., van den Eertwegh, Alfons J. M., Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Boers‐Sonderen, Marye J., de Groot, Jan Willem W. B., Hospers, Geke A. P., Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense‐den Boer, Marion, Verheijden, Rik J., van der Veldt, Astrid A. M., Wouters, Michel W. J. M., Blokx, Willeke A. M., and Suijkerbuijk, Karijn P. M.

Subjects
*IPILIMUMAB, *PROPORTIONAL hazards models, *BRAF genes, *MELANOMA, *LACTATE dehydrogenase
Abstract

Background: Effectivity of BRAF(/MEK) inhibitor rechallenge has been described in prior studies. However, structured data are largely lacking. Methods: Data from all advanced melanoma patients treated with BRAFi(/MEKi) rechallenge were retrieved from the Dutch Melanoma Treatment Registry. The authors analyzed objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS) for both first treatment and rechallenge. They performed a multivariable logistic regression and a multivariable Cox proportional hazards model to assess factors associated with response and survival. Results: The authors included 468 patients in the largest cohort to date who underwent at least two treatment episodes of BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS was 4.6 months (95% confidence interval [CI], 4.1–5.2), and median OS was 8.2 months (95% CI, 7.2–9.4). Median PFS after rechallenge for patients who discontinued first BRAFi(/MEKi) treatment due to progression was 3.1 months (95% CI, 2.7–4.0) versus 5.2 months (95% CI, 4.5–5.9) for patients who discontinued treatment for other reasons. Discontinuing first treatment due to progression and lactate dehydrogenase (LDH) levels greater than two times the upper limit of normal were associated with lower odds of response and worse PFS and OS. Symptomatic brain metastases were associated with worse survival, whereas a longer treatment interval between first treatment and rechallenge was associated with better survival. Responding to the first BRAFi(/MEKi) treatment was not associated with response or survival. Conclusions: This study confirms that patients benefit from rechallenge. Elevated LDH levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit from rechallenge. A prolonged treatment interval is associated with more benefit from rechallenge. This study confirms that patients with advanced melanoma derive benefit from rechallenge with BRAFi(/MEKi). Elevated lactate dehydrogenase levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit on rechallenge. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands

Author

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

Subjects
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.

Published
2023

14. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Author

Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Medical Oncology, Erasmus MC other, Internal medicine, Medical oncology, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Cancer Research, OUTCOMES, Survival, CANCERS, CHRONIC LYMPHOCYTIC-LEUKEMIA, Response, Haematologic malignancy, SOLID TUMORS, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Immune checkpoint inhibitors, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Oncology, CELLS, IMMUNOTHERAPY, Melanoma
Abstract

Background: Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease-or treatment-related T-or B-cell dysfunction.Methods: All advanced melanoma patients treated with anti-PD-1-based treatment or tar-geted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific sur-vival (MSS) were analysed for patients with HM (HM+) and without HM (HM-). A cox model was used to account for confounders associated with PFS and MSS.Results: In total, 4638 advanced melanoma patients received first-line anti-PD-1 mono -therapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated pa-tients, the median PFS was 2.8 months for HM+ and 9.9 months for HM- (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM- (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HRadj 1.62; 95% confidence interval [95% CI] 1.15-2.29; p = 0.006) and melanoma-related death (HRadj 1.74; 95% CI 1.09-2.78; p = 0.020). Median PFS and MSS for first-line BRAF (/MEK-) inhibitor-treated HM+ and HM- patients were not significantly different.Conclusions: Patients with HM and advanced melanoma show significantly worse melanoma -related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2023

16. Adjuvant treatment of in‐transit melanoma: Narrowing the knowledge gap left by clinical trials

Author

de Meza, Melissa M., primary, Blokx, Willeke A. M., additional, Bonenkamp, Han J., additional, Blank, Cristian U., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Boers‐Sonderen, Marye J., additional, de Groot, Jan Willem B., additional, Haanen, John B., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen W., additional, van Not, Olivier J., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Stevense‐Den Boer, Marion A., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, van den Eertwegh, Alfons J. M., additional, Suijkerbuijk, Karijn P. M., additional, and Wouters, Michel W. J. M., additional

Published
2023
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17. Adjuvant treatment of in-transit melanoma:Narrowing the knowledge gap left by clinical trials

Author

de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M

Abstract

Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P < .01). Locoregional metastases occurred as first recurrence in 38.9% nodal disease only, 71.9% of ITM-only and 44.0% of ITM and nodal disease patients. Distant recurrences occurred in 42.3%, 18.8% and 36.0%, respectively (P = .02). 12-months OS was not significantly different for nodal disease only patients compared with ITM-only (94.4% vs 97.6%, P = .06) but was significantly higher for ITM-only compared with ITM and nodal disease patients (97.6% vs 91.0%, P < .01). In conclusion, we showed that in the adjuvant setting, RFS rates in ITM-only patients are similar to non-ITM, though better than in ITM and nodal disease patients. Adjuvant-treated ITM-only patients less often experience distant recurrences and have a superior OS compared with ITM and nodal disease patients.

Published
2023

18. Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands

Author

MS Medische Oncologie, Cancer, Infection & Immunity, 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, MS Medische Oncologie, Cancer, Infection & Immunity, 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, and van den Eertwegh, Alfons J M

Published
2023

19. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Author

MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, and Blokx, Willeke A M

Published
2023

20. Adjuvant Treatment of In-Transit Melanoma: Narrowing the Knowledge Gap Left by Clinical Trials

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M

Published
2023

21. ASO Visual Abstract: Is a History of Optimal Staging by SLNB in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2023

22. Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2023

24. ASO Visual Abstract: Is a History of Optimal Staging by SLNB in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Blankenstein, Stephanie A., primary, Bonenkamp, Johannes J., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Blokx, Willeke A. M., additional, Boers-Sonderen, Marye J., additional, van den Eertwegh, Alfons J. M., additional, Franken, Margreet G., additional, de Groot, Jan Willem B., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen W., additional, van Not, Olivier J., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Suijkerbuijk, Karijn P. M., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Westgeest, Hans M., additional, Wouters, Michel W. J. M., additional, and van Akkooi, Alexander C. J., additional

Published
2022
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25. A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial

Author

van Dodewaard-de Jong, Joyce M., de Klerk, John M. H., Bloemendal, Haiko J., Oprea-Lager, Daniela E., Hoekstra, Otto S., van den Berg, H. Pieter, Los, Maartje, Beeker, Aart, Jonker, Marianne A., O’Sullivan, Joe M., Verheul, Henk M. W., and van den Eertwegh, Alfons J. M.

Published
2017
Full Text
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26. Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Blankenstein, Stephanie A., primary, Bonenkamp, Johannes J., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Blokx, Willeke A. M., additional, Boers-Sonderen, Marye J., additional, van den Eertwegh, Alfons J. M., additional, Franken, Margreet G., additional, de Groot, Jan Willem B., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen W., additional, van Not, Olivier J., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Suijkerbuijk, Karijn P. M., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Westgeest, Hans M., additional, Wouters, Michel W. J. M., additional, and van Akkooi, Alexander C. J., additional

Published
2022
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28. Local delivery of low-dose anti–CTLA-4 to the melanoma lymphatic basin leads to systemic T reg reduction and effector T cell activation

Author

van Pul, Kim M., primary, Notohardjo, Jessica C. L., additional, Fransen, Marieke F., additional, Koster, Bas D., additional, Stam, Anita G. M., additional, Chondronasiou, Dafni, additional, Lougheed, Sinéad M., additional, Bakker, Joyce, additional, Kandiah, Vinitha, additional, van den Tol, M. Petrousjka, additional, Jooss, Karin, additional, Vuylsteke, Ronald J. C. L. M., additional, van den Eertwegh, Alfons J. M., additional, and de Gruijl, Tanja D., additional

Published
2022
Full Text
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29. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author

Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G

Abstract

Background Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. Methods In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. Results A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. Conclusions In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than amon

Published
2022

30. Response to immune checkpoint inhibitors in acral melanoma:A nationwide cohort study

Author

van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Abstract

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

Published
2022

31. End-of-Life Use of Systemic Therapy in Patients With Advanced Melanoma: A Nationwide Cohort Study

Author

van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, 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, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, van den Eertwegh, Alfons J M, van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, 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, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, and van den Eertwegh, Alfons J M

Abstract

PURPOSE: The introduction of immune checkpoint inhibitors and targeted therapies improved the overall survival of patients with advanced melanoma. It is not known how often these costly treatments with potential serious side effects are ineffectively applied in the last phase of life. This study aimed to investigate the start of a new systemic therapy within 45 and 90 days of death in Dutch patients with advanced melanoma.METHODS: We selected patients who were diagnosed with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry, and died between 2013 and 2019. Primary outcome was the probability of starting a new systemic therapy 45 and 90 days before death. Secondary outcomes were type of systemic therapy started, grade 3/4 adverse events (AEs), and the total costs of systemic therapies.RESULTS: Between 2013 and 2019, 3,797 patients with unresectable IIIC or stage IV melanoma were entered in the registry and died. The percentage of patients receiving a new systemic therapy within 45 and 90 days before death was significantly different between Dutch melanoma centers (varying from 6% to 23% and 20% to 46%, respectively). Thirteen percent of patients (n = 146) developed grade 3/4 AEs in the last period before death. The majority of patients with an AE required hospital admission (n = 102, 69.6%). Mean total costs of systemic therapy per cohort year of the patients who received a new systemic therapy within 90 days before death were 2.3%-2.8% of the total costs spent on melanoma therapies.CONCLUSION: The minority of Dutch patients with metastatic melanoma started a new systemic therapy in the last phase of life. However, the percentages varied between Dutch melanoma centers. Financial impact of these therapies in the last phase of life is relatively small.

Published
2022

32. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author

HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G

Published
2022

33. BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, 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, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, 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, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2022

34. Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2022

35. Discontinuation of anti-PD-1 monotherapy in advanced melanoma - outcomes of daily clinical practice

Author

MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Wouters, Michel W J M, de Wreede, Liesbeth C, 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, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Jacobus J M, Haanen, John B A G, MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Wouters, Michel W J M, de Wreede, Liesbeth C, 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, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Jacobus J M, and Haanen, John B A G

Published
2022

39. Long-Term Survival in Patients With Advanced Melanoma.

Author

van Not, Olivier J., van den Eertwegh, Alfons J. M., Jalving, Hilde, Bloem, Manja, Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Boers-Sonderen, Marye J., de Groot J. W. B., Jan Willem, Hospers, Geke A. P., Kapiteijn, Ellen, Leeneman, Brenda, D., Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A. M., Vreugdenhil G., Gerard, Wouters, Michel W. J. M., and Blokx, Willeke A. M.

Published
2024
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40. CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

Author

Affandi, Alsya J., primary, Olesek, Katarzyna, additional, Grabowska, Joanna, additional, Nijen Twilhaar, Maarten K., additional, Rodríguez, Ernesto, additional, Saris, Anno, additional, Zwart, Eline S., additional, Nossent, Esther J., additional, Kalay, Hakan, additional, de Kok, Michael, additional, Kazemier, Geert, additional, Stöckl, Johannes, additional, van den Eertwegh, Alfons J. M., additional, de Gruijl, Tanja D., additional, Garcia-Vallejo, Juan J., additional, Storm, Gert, additional, van Kooyk, Yvette, additional, and den Haan, Joke M. M., additional

Published
2021
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41. CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

Author

Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Olesek, Katarzyna, Grabowska, Joanna, Nijen Twilhaar, Maarten K, Rodríguez, Ernesto, Saris, Anno, Zwart, Eline S, Nossent, Esther J, Kalay, Hakan, de Kok, Michael, Kazemier, Geert, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Garcia-Vallejo, Juan J, Storm, Gert, van Kooyk, Yvette, den Haan, Joke M M, Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Olesek, Katarzyna, Grabowska, Joanna, Nijen Twilhaar, Maarten K, Rodríguez, Ernesto, Saris, Anno, Zwart, Eline S, Nossent, Esther J, Kalay, Hakan, de Kok, Michael, Kazemier, Geert, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Garcia-Vallejo, Juan J, Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M M

Published
2021

42. Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

Author

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

Published
2021

43. Local delivery of low-dose anti–CTLA-4 to the melanoma lymphatic basin leads to systemic Treg reduction and effector T cell activation.

Author

van Pul, Kim M., Notohardjo, Jessica C. L., Fransen, Marieke F., Koster, Bas D., Stam, Anita G. M., Chondronasiou, Dafni, Lougheed, Sinéad M., Bakker, Joyce, Kandiah, Vinitha, van den Tol, M. Petrousjka, Jooss, Karin, Vuylsteke, Ronald J. C. L. M., van den Eertwegh, Alfons J. M., and de Gruijl, Tanja D.

Subjects
T cells, SENTINEL lymph node biopsy, REGULATORY T cells, SENTINEL lymph nodes, T cell differentiation, MELANOMA
Abstract

Preclinical studies show that locoregional CTLA-4 blockade is equally effective in inducing tumor eradication as systemic delivery, without the added risk of immune-related side effects. This efficacy is related to access of the CTLA-4 blocking antibodies to tumor-draining lymph nodes (TDLNs). Local delivery of anti–CTLA-4 after surgical removal of primary melanoma, before sentinel lymph node biopsy (SLNB), provides a unique setting to clinically assess the role of TDLN in the biological efficacy of locoregional CTLA-4 blockade. Here, we have evaluated the safety, tolerability, and immunomodulatory effects in the SLN and peripheral blood of a single dose of tremelimumab [a fully human immunoglobulin gamma-2 (IgG2) mAb directed against CTLA-4] in a dose range of 2 to 20 mg, injected intradermally at the tumor excision site 1 week before SLNB in 13 patients with early-stage melanoma (phase 1 trial; NCT04274816). Intradermal delivery was safe and well tolerated and induced activation of migratory dendritic cell (DC) subsets in the SLN. It also induced profound and durable decreases in regulatory T cell (Treg) frequencies and activation of effector T cells in both SLN and peripheral blood. Moreover, systemic T cell responses against NY-ESO-1 or MART-1 were primed or boosted (N = 7), in association with T cell activation and central memory T cell differentiation. These findings indicate that local administration of anti–CTLA-4 may offer a safe and promising adjuvant treatment strategy for patients with early-stage melanoma. Moreover, our data demonstrate a central role for TDLN in the biological efficacy of CTLA-4 blockade and support TDLN-targeted delivery methods. Under the skin: Although systemic immune checkpoint blockade (ICB) displays therapeutic efficacy in cancers, it induces immune-related adverse events (irAEs). Avoiding irAEs is crucial for effective ICB. Van Pul et al. performed a phase 1 clinical trial testing the effects of an intradermal injection of anti–CTLA-4 at the site of primary tumor excision in patients with early-stage melanoma. Seven of 13 patients immunologically responded to the treatment, with little to no irAEs. Responders had more tumor antigen–specific T cells in the blood, increased migratory DC activation in the sentinel lymph node (SLN), and decreased Tregs in both the SLN and blood. Thus, intradermal anti–CTLA-4 after primary tumor excision in melanoma induced a favorable immune response and has promise as a treatment option for patients with early-stage melanoma. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Author

Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, van Akkooi, Alexander C J, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2020

45. Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs

Author

Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, Franken, Margreet G, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, and Franken, Margreet G

Published
2020

46. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Author

Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Grabowska, Joanna, Olesek, Katarzyna, Lopez Venegas, Miguel, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P G, Pijffers, Helen J, Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S, Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Storm, Gert, van Kooyk, Yvette, den Haan, Joke M M, Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Grabowska, Joanna, Olesek, Katarzyna, Lopez Venegas, Miguel, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P G, Pijffers, Helen J, Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S, Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M M

Published
2020

47. Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Author

MS Medische Oncologie, Infection & Immunity, Cancer, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, van Akkooi, Alexander C J, MS Medische Oncologie, Infection & Immunity, Cancer, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2020

48. Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs

Author

MS Medische Oncologie, Infection & Immunity, Cancer, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, Franken, Margreet G, MS Medische Oncologie, Infection & Immunity, Cancer, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, and Franken, Margreet G

Published
2020

49. Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study

Author

MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, Haanen, John B A G, Wouters, Michel W J M, de Wreede, Liesbeth C, Jochems, Anouk, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen W, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Koos J M, van den Eertwegh, Alfons J M, MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, Haanen, John B A G, Wouters, Michel W J M, de Wreede, Liesbeth C, Jochems, Anouk, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen W, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Koos J M, and van den Eertwegh, Alfons J M

Published
2020

50. Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands.

Author

Kuppen, Malou C. P., Westgeest, Hans M., van den Eertwegh, Alfons J. M., van Moorselaar, Reindert J. A., van Oort, Inge M., Tascilar, Metin, Mehra, Niven, Lavalaye, Jules, Somford, Diederik M., Aben, Katja K. H., Bergman, Andre M., de Wit, Ronald, van den Bergh, A. C. M. (Fons), Uyl-de Groot, Carin A., and Gerritsen, Winald R.

Subjects
CASTRATION-resistant prostate cancer, BONE health, DISEASE incidence, DENOSUMAB
Abstract

Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of developing symptomatic skeletal events (SSEs). We retrospectively investigated incidence of SSEs and the use of bone health agents (BHA) in a contemporary, treated bone metastatic CRPC population. Although patients with early BHA use had lower incidence rates of SSE and longer SSE-free survival, there was an undertreatment with BHAs in our population. Especially in patients with risk factors as pain and/or opioid use and prior SSE, timely initiation of BHAs is recommended. Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. Patients and Methods: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. Results: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001). Conclusion: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE. [ABSTRACT FROM AUTHOR]

Published
2022
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