28 results on '"Boers-Sonderen, Marye J."'
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2. Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021
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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.
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- 2024
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3. 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?
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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
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- 2024
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4. Adjuvant treatment with anti‐PD‐1 in acral melanoma: A nationwide study.
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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.
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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]
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- 2024
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5. Baseline and on Treatment Biodistribution Variability of 18F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication
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MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, and Haanen, John B A G
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- 2024
6. Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma
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Medisch Oncologische Disciplines, Hart- en Vaatziekten Team A, MS Medische Oncologie, Cancer, CTI, Epi Kanker, JC onderzoeksprogramma Kanker, Infection & Immunity, Verheijden, Rik J., Burgers, Femke H., Janssen, Josephine C., Putker, Anouk E., Veenstra, Sophie P.G.R., Hospers, Geke A.P., Aarts, Maureen J.B., Hehenkamp, Karel W., Doornebosch, Veerle L.E., Verhaert, Marthe, van den Berkmortel, Franchette W.P.J., Chatzidionysiou, Katerina, Llobell, Arturo, Barros, Milton, Maria, Alexandre T.J., Takeji, Akari, García Morillo, José Salvador, Lidar, Merav, van Eijs, Mick J.M., Blank, Christian U., Aspeslagh, Sandrine, Piersma, Djura, Kapiteijn, Ellen, Labots, Mariette, Boers-Sonderen, Marye J., van der Veldt, Astrid A.M., Haanen, John B.A.G., May, Anne M., Suijkerbuijk, Karijn P.M., Medisch Oncologische Disciplines, Hart- en Vaatziekten Team A, MS Medische Oncologie, Cancer, CTI, Epi Kanker, JC onderzoeksprogramma Kanker, Infection & Immunity, Verheijden, Rik J., Burgers, Femke H., Janssen, Josephine C., Putker, Anouk E., Veenstra, Sophie P.G.R., Hospers, Geke A.P., Aarts, Maureen J.B., Hehenkamp, Karel W., Doornebosch, Veerle L.E., Verhaert, Marthe, van den Berkmortel, Franchette W.P.J., Chatzidionysiou, Katerina, Llobell, Arturo, Barros, Milton, Maria, Alexandre T.J., Takeji, Akari, García Morillo, José Salvador, Lidar, Merav, van Eijs, Mick J.M., Blank, Christian U., Aspeslagh, Sandrine, Piersma, Djura, Kapiteijn, Ellen, Labots, Mariette, Boers-Sonderen, Marye J., van der Veldt, Astrid A.M., Haanen, John B.A.G., May, Anne M., and Suijkerbuijk, Karijn P.M.
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- 2024
7. Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients
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MS Medische Oncologie, Cancer, Infection & Immunity, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A J M van den, Haanen, John B, Aarts, Maureen J B, Berkmortel, Franchette W P J van den, Blank, Christiaan U, Boers-Sonderen, Marye J, Groot, Jan Willem B de, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, A M, Veldt, Astrid A M van der, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Kapiteijn, Ellen, MS Medische Oncologie, Cancer, Infection & Immunity, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A J M van den, Haanen, John B, Aarts, Maureen J B, Berkmortel, Franchette W P J van den, Blank, Christiaan U, Boers-Sonderen, Marye J, Groot, Jan Willem B de, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, A M, Veldt, Astrid A M van der, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, and Kapiteijn, Ellen
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- 2024
8. Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study
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Cancer, MS Medische Oncologie, Medisch Oncologische Disciplines, Pathologie Pathologen staf, Infection & Immunity, 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., Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., Cancer, MS Medische Oncologie, Medisch Oncologische Disciplines, Pathologie Pathologen staf, Infection & Immunity, 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., Suijkerbuijk, Karijn P.M., and Wouters, Michel W.J.M.
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- 2024
9. Long-Term Survival in Patients With Advanced Melanoma
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MS Medische Oncologie, Cancer, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Groningen, University, 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, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, MS Medische Oncologie, Cancer, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Groningen, University, 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, Blokx, Willeke A M, and Suijkerbuijk, Karijn P M
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- 2024
10. Adjuvant treatment with anti-PD-1 in acral melanoma:A nationwide study
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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., Suijkerbuijk, Karijn P. M., Wouters, Michel W. J. M., 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., Suijkerbuijk, Karijn P. M., and Wouters, Michel W. J. M.
- 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.
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- 2024
11. Long-Term Survival in Patients With Advanced Melanoma
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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., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., 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., Blokx, Willeke A.M., and Suijkerbuijk, Karijn P.M.
- Abstract
IMPORTANCE: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival. OBJECTIVE: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023. EXPOSURES: Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab. MAIN OUTCOMES AND MEASURES: Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR).RESULTS: A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69). CONCLUSIONS AND RELEVANCE: This cohort study of
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- 2024
12. Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients
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Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A. J.M.van den, Haanen, John B., Aarts, Maureen J.B., Berkmortel, Franchette W.P.J.van den, Blank, Christiaan U., Boers-Sonderen, Marye J., Groot, Jan Willem B.de, Hospers, Geke A.P., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, A. M., Veldt, Astrid A.M.van der, Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., Kapiteijn, Ellen, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A. J.M.van den, Haanen, John B., Aarts, Maureen J.B., Berkmortel, Franchette W.P.J.van den, Blank, Christiaan U., Boers-Sonderen, Marye J., Groot, Jan Willem B.de, Hospers, Geke A.P., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, A. M., Veldt, Astrid A.M.van der, Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., and Kapiteijn, Ellen
- Abstract
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in a
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- 2024
13. BRAF/MEK inhibitor rechallenge in advanced melanoma patients
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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., Suijkerbuijk, Karijn P.M., 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.
- 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.
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- 2024
14. A prediction model for response to immune checkpoint inhibition in advanced melanoma
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van Duin, Isabella A. J., Verheijden, Rik J., van Diest, Paul J., Blokx, Willeke A. M., El-Sharouni, Mary-Ann, Verhoeff, Joost J. C., Leiner, Tim, van den Eertwegh, Alfonsus J. M., de Groot, Jan Willem B., van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Haanen, John B. A. G., Hospers, Geke A. P., Piersma, Djura, van Rijn, Rozemarijn S., van Der Veldt, Astrid A. M., Vreugdenhil, Gerard, Wouters, Michel W. J. M., Stevense-den Boer, Marion A. M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, Suijkerbuijk, Karijn P. M., Elias, Sjoerd G., van Duin, Isabella A. J., Verheijden, Rik J., van Diest, Paul J., Blokx, Willeke A. M., El-Sharouni, Mary-Ann, Verhoeff, Joost J. C., Leiner, Tim, van den Eertwegh, Alfonsus J. M., de Groot, Jan Willem B., van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Haanen, John B. A. G., Hospers, Geke A. P., Piersma, Djura, van Rijn, Rozemarijn S., van Der Veldt, Astrid A. M., Vreugdenhil, Gerard, Wouters, Michel W. J. M., Stevense-den Boer, Marion A. M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, Suijkerbuijk, Karijn P. M., and Elias, Sjoerd G.
- Abstract
Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal–external cross-validation. Included patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence—all at start of ICI—, and location and type of primary melanoma, the presence of satellites and/or in-transit metastases at primary diagnosis and sex. The over-optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64–0.66). The range of predicted response probabilities was 7%–81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression-free survival (20.0 vs 2.8 months; P <.001) and median overall survival (62.0 vs 8.0 months; P <.001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.
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- 2024
15. A prediction model for response to immune checkpoint inhibition in advanced melanoma
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Cancer, MS Medische Oncologie, Pathologie, Pathologie Pathologen staf, Pathologie Groep Van Diest, MS Radiotherapie, Brain, Circulatory Health, MS Radiologie, Infection & Immunity, Epi Kanker Team C, JC onderzoeksprogramma Kanker, van Duin, Isabella A J, Verheijden, Rik J, van Diest, Paul J, Blokx, Willeke A M, El-Sharouni, Mary-Ann, Verhoeff, Joost J C, Leiner, Tim, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, Suijkerbuijk, Karijn P M, Elias, Sjoerd G, Cancer, MS Medische Oncologie, Pathologie, Pathologie Pathologen staf, Pathologie Groep Van Diest, MS Radiotherapie, Brain, Circulatory Health, MS Radiologie, Infection & Immunity, Epi Kanker Team C, JC onderzoeksprogramma Kanker, van Duin, Isabella A J, Verheijden, Rik J, van Diest, Paul J, Blokx, Willeke A M, El-Sharouni, Mary-Ann, Verhoeff, Joost J C, Leiner, Tim, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, Suijkerbuijk, Karijn P M, and Elias, Sjoerd G
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- 2024
16. 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?
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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
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- 2024
17. BRAF/MEK inhibitor rechallenge in advanced melanoma patients
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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
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- 2024
18. Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021
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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
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- 2024
19. Adjuvant dendritic cell therapy in stage IIIB/C melanoma:the MIND-DC randomized phase III trial
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Bol, Kalijn F., Schreibelt, Gerty, Bloemendal, Martine, van Willigen, Wouter W., Hins-de Bree, Simone, de Goede, Anna L., de Boer, Annemiek J., Bos, Kevin J.H., Duiveman-de Boer, Tjitske, Olde Nordkamp, Michel A.M., van Oorschot, Tom G.M., Popelier, Carlijn J., Pots, Jeanne M., Scharenborg, Nicole M., van de Rakt, Mandy W.M.M., de Ruiter, Valeska, van Meeteren, Wilmy S., van Rossum, Michelle M., Croockewit, Sandra J., Koeneman, Bouke J., Creemers, Jeroen H.A., Wortel, Inge M.N., Angerer, Caroline, Brüning, Mareke, Petry, Katja, Dzionek, Andrzej, van der Veldt, Astrid A., van Grünhagen, Dirk J., Werner, Johanna E.M., Bonenkamp, Johannes J., Haanen, John B.A.G., Boers-Sonderen, Marye J., Koornstra, Rutger H.T., Boomsma, Martijn F., Aarntzen, Erik H.J., Gotthardt, Martin, Nagarajah, James, de Witte, Theo J.M., Figdor, Carl G., de Wilt, Johannes H.W., Textor, Johannes, de Groot, Jan Willem B., Gerritsen, Winald R., de Vries, I. Jolanda M., Bol, Kalijn F., Schreibelt, Gerty, Bloemendal, Martine, van Willigen, Wouter W., Hins-de Bree, Simone, de Goede, Anna L., de Boer, Annemiek J., Bos, Kevin J.H., Duiveman-de Boer, Tjitske, Olde Nordkamp, Michel A.M., van Oorschot, Tom G.M., Popelier, Carlijn J., Pots, Jeanne M., Scharenborg, Nicole M., van de Rakt, Mandy W.M.M., de Ruiter, Valeska, van Meeteren, Wilmy S., van Rossum, Michelle M., Croockewit, Sandra J., Koeneman, Bouke J., Creemers, Jeroen H.A., Wortel, Inge M.N., Angerer, Caroline, Brüning, Mareke, Petry, Katja, Dzionek, Andrzej, van der Veldt, Astrid A., van Grünhagen, Dirk J., Werner, Johanna E.M., Bonenkamp, Johannes J., Haanen, John B.A.G., Boers-Sonderen, Marye J., Koornstra, Rutger H.T., Boomsma, Martijn F., Aarntzen, Erik H.J., Gotthardt, Martin, Nagarajah, James, de Witte, Theo J.M., Figdor, Carl G., de Wilt, Johannes H.W., Textor, Johannes, de Groot, Jan Willem B., Gerritsen, Winald R., and de Vries, I. Jolanda M.
- Abstract
Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88−1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73−2.38; p = 0.44). Grade 3−4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed.
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- 2024
20. Improving survival in advanced melanoma patients:a trend analysis from 2013 to 2021
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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., 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.
- Abstract
Background: The prognosis of advanced melanoma patients has significantly improved over the years. We aimed to evaluate the survival per year of diagnosis. Methods: All systemically treated patients diagnosed with advanced melanoma from 2013 to 2021 were included from the Dutch Melanoma Treatment Registry. Baseline characteristics and overall survival (OS) were compared between the different years of diagnosis. A multivariable Cox proportional hazards model was used to estimate the association between year of diagnosis and OS. Findings: For this cohort study, we included 6260 systemically treated advanced melanoma patients. At baseline, there was an increase over the years in age, the percentage of patients with an ECOG PS ≥ 2, with brain metastases, and a synchronous diagnosis of primary and unresectable melanoma. Median OS increased from 11.2 months (95% CI 10.0–12.4) for patients diagnosed in 2013 to 32.0 months (95% CI 26.6–36.7) for patients diagnosed in 2019. Median OS was remarkably lower for patients diagnosed in 2020 (26.6 months; 95% CI 23.9–35.1) and 2021 (24.0 months; 95% CI 20.4-NR). Patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019, although this was not significant. The multivariable Cox regression showed a lower hazard of death for the years of diagnosis after 2013. In contrast, patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019. Interpretation: After a continuous survival improvement for advanced melanoma patients between 2013 and 2019, outcomes of patients diagnosed in 2020 and 2021 seem poorer. This trend of decreased survival remained after correcting for known prognostic factors and previous neoadjuvant or adjuvant treatment, suggesting that it is explained by unmeasured factors, which—considering the timing—could be COVID-19-related. Funding
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- 2024
21. Baseline and on Treatment Biodistribution Variability of 18F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication.
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van der Hiel, Bernies, Aalbersberg, Else A., van den Eertwegh, Alfons J. M., Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y. F. L., Boers-Sonderen, Marye J., Stokkel, Marcel P. M., de Wit-van der Veen, Linda J., and Haanen, John B. A. G.
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- 2024
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22. Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial
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Bol, Kalijn F., primary, Schreibelt, Gerty, additional, Bloemendal, Martine, additional, van Willigen, Wouter W., additional, Hins-de Bree, Simone, additional, de Goede, Anna L., additional, de Boer, Annemiek J., additional, Bos, Kevin J. H., additional, Duiveman-de Boer, Tjitske, additional, Olde Nordkamp, Michel A. M., additional, van Oorschot, Tom G. M., additional, Popelier, Carlijn J., additional, Pots, Jeanne M., additional, Scharenborg, Nicole M., additional, van de Rakt, Mandy W. M. M., additional, de Ruiter, Valeska, additional, van Meeteren, Wilmy S., additional, van Rossum, Michelle M., additional, Croockewit, Sandra J., additional, Koeneman, Bouke J., additional, Creemers, Jeroen H. A., additional, Wortel, Inge M. N., additional, Angerer, Caroline, additional, Brüning, Mareke, additional, Petry, Katja, additional, Dzionek, Andrzej, additional, van der Veldt, Astrid A., additional, van Grünhagen, Dirk J., additional, Werner, Johanna E. M., additional, Bonenkamp, Johannes J., additional, Haanen, John B. A. G., additional, Boers-Sonderen, Marye J., additional, Koornstra, Rutger H. T., additional, Boomsma, Martijn F., additional, Aarntzen, Erik H. J., additional, Gotthardt, Martin, additional, Nagarajah, James, additional, de Witte, Theo J. M., additional, Figdor, Carl G., additional, de Wilt, Johannes H. W., additional, Textor, Johannes, additional, de Groot, Jan Willem B., additional, Gerritsen, Winald R., additional, and de Vries, I. Jolanda M., additional
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- 2024
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23. A prediction model for response to immune checkpoint inhibition in advanced melanoma
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van Duin, Isabella A. J., primary, Verheijden, Rik J., additional, van Diest, Paul J., additional, Blokx, Willeke A. M., additional, El‐Sharouni, Mary‐Ann, additional, Verhoeff, Joost J. C., additional, Leiner, Tim, additional, van den Eertwegh, Alfonsus J. M., additional, de Groot, Jan Willem B., additional, van Not, Olivier J., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, Stevense‐den Boer, Marion A. M., additional, Boers‐Sonderen, Marye J., additional, Kapiteijn, Ellen, additional, Suijkerbuijk, Karijn P. M., additional, and Elias, Sjoerd G., additional
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- 2024
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24. BRAF/MEK inhibitor rechallenge in advanced melanoma patients
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Van Not, Olivier J., primary, van den Eertwegh, Alfons J. M., additional, Haanen, John B., additional, van Rijn, Rozemarijn S., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Boers‐Sonderen, Marye J., additional, de Groot, Jan Willem W. B., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Bloem, Manja, additional, Piersma, Djura, additional, Stevense‐den Boer, Marion, additional, Verheijden, Rik J., additional, van der Veldt, Astrid A. M., additional, Wouters, Michel W. J. M., additional, Blokx, Willeke A. M., additional, and Suijkerbuijk, Karijn P. M., additional
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- 2024
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25. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma.
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Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda M, Hoeijmakers LL, Saw RPM, Lijnsvelt JM, Maher NG, Pulleman SM, Gonzalez M, Torres Acosta A, van Houdt WJ, Lo SN, Kuijpers AMJ, Spillane A, Klop WMC, Pennington TE, Zuur CL, Shannon KF, Seinstra BA, Rawson RV, Haanen JBAG, Ch'ng S, Naipal KAT, Stretch J, van Thienen JV, Rtshiladze MA, Wilgenhof S, Kapoor R, Meerveld-Eggink A, Grijpink-Ongering LG, van Akkooi ACJ, Reijers ILM, Gyorki DE, Grünhagen DJ, Speetjens FM, Vliek SB, Placzke J, Spain L, Stassen RC, Amini-Adle M, Lebbé C, Faries MB, Robert C, Ascierto PA, van Rijn R, van den Berkmortel FWPJ, Piersma D, van der Westhuizen A, Vreugdenhil G, Aarts MJB, Stevense-den Boer MAM, Atkinson V, Khattak M, Andrews MC, van den Eertwegh AJM, Boers-Sonderen MJ, Hospers GAP, Carlino MS, de Groot JB, Kapiteijn E, Suijkerbuijk KPM, Rutkowski P, Sandhu S, van der Veldt AAM, and Long GV
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Chemotherapy, Adjuvant methods, Chemotherapy, Adjuvant statistics & numerical data, Disease-Free Survival, Kaplan-Meier Estimate, Progression-Free Survival, Young Adult, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Ipilimumab administration & dosage, Ipilimumab adverse effects, Ipilimumab therapeutic use, Melanoma mortality, Melanoma pathology, Melanoma therapy, Neoadjuvant Therapy methods, Neoadjuvant Therapy statistics & numerical data, Neoplasm Staging, Nivolumab therapeutic use, Nivolumab adverse effects, Nivolumab administration & dosage, Skin Neoplasms mortality, Skin Neoplasms pathology, Skin Neoplasms therapy
- Abstract
Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy., Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival., Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group., Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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26. Baseline and on Treatment Biodistribution Variability of 18 F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication.
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van der Hiel B, Aalbersberg EA, van den Eertwegh AJM, Fischer J, Boellaard R, de Vos FYFL, Boers-Sonderen MJ, Stokkel MPM, de Wit-van der Veen LJ, and Haanen JBAG
- Subjects
- Humans, Tissue Distribution, Middle Aged, Male, Female, Aged, Adult, Neoplasm Staging, Biological Transport, Melanoma diagnostic imaging, Melanoma drug therapy, Melanoma metabolism, Positron Emission Tomography Computed Tomography, Dideoxynucleosides pharmacokinetics
- Abstract
Purpose: This prospective study evaluates the biodistribution of 18 F-FLT PET in patients with advanced melanoma before and after treatment with BRAF/MEK inhibitors., Patients and Methods: Eighteen BRAF-positive unresectable stage IIIc or IV melanoma patients referred for 18 F-FLT PET/CT before (BL) and during (D14) BRAF/MEK inhibition were included. 18 F-FLT accumulation in the liver, bone marrow, blood, and muscle was quantified., Results: Baseline interpatient 18 F-FLT uptake had a coefficient-of-variation between 17.5% and 21.5%. During treatment, liver uptake increased (SUV meanBL = 4.86 ± 0.98, SUV meanD14 = 6.31 ± 1.36, P < 0.001) and bone marrow uptake decreased (SUV meanBL = 7.67 ± 1.65, SUV meanD14 = 6.78 ± 1.19, P < 0.025). Both changes were unrelated to baseline metabolic tumor volume or tumor response., Conclusions: To assess 18 F-FLT PET, both liver and bone marrow uptake may be used as normal tissue references at baseline, but 18 F-FLT biodistribution significantly changes in longitudinal response studies when treated with BRAF/MEK inhibitors., Competing Interests: Conflicts of interest and sources of funding: A.J.M.v.d.E. received study grant from Sanofi, Roche, Bristol Myers Squibb, TEVA, and Idera; received travel expenses coverage from MSD Oncology, Roche, Pfizer, and Sanofi; received speaker honoraria from Bristol Myers Squibb and Novartis; and is part of the advisory board of Bristol Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, and Merck, Pierre Fabre. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer, all paid to institute, as well as received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. F.Y.F.L.d.V. received research grant from Foundation STOPBraintumors.org , Bristol Myers Squibb, Novartis, Servier, CureVac, and EORTC, all paid to institute. J.B.A.G.H. has advisory roles for Bristol Myers Squibb, CureVac, GSK, Ipsen, Iovance Biotherapeutics, Imcyse, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche, Sanofi, and Third Rock Ventures; is a member of SAB of Achilles Tx, BioNTech, Gadeta, Immunocore, Instil Bio, PokeAcell, Scenic, T-Knife, and Neogene Tx, all paid to institute except Neogene Tx and Scenic; and received grant support from Amgen, Asher Bio, BioNTech, Bristol Myers Squibb, MSD, Novartis, and Sastra Cell Therapy, all paid to institute. The other authors declare no conflicts of interest. This work was supported by an unrestricted grant by Roche Medical B.V. The company has approved the design of the study and provided cobimetinib free of charge. The company has no role in collection, analysis, and interpretation of data or in writing the manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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27. Long-Term Survival in Patients With Advanced Melanoma.
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van Not OJ, van den Eertwegh AJM, Jalving H, Bloem M, Haanen JB, van Rijn RS, Aarts MJB, van den Berkmortel FWPJ, Blank CU, Boers-Sonderen MJ, de Groot J W B JW, Hospers GAP, Kapiteijn E, Leeneman B, D P, Stevense-den Boer M, van der Veldt AAM, Vreugdenhil G G, Wouters MWJM, Blokx WAM, and Suijkerbuijk KPM
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- Humans, Male, Female, Middle Aged, Aged, Netherlands epidemiology, Ipilimumab therapeutic use, Nivolumab therapeutic use, Skin Neoplasms drug therapy, Skin Neoplasms mortality, Skin Neoplasms pathology, Cohort Studies, Registries, Progression-Free Survival, Prospective Studies, Melanoma drug therapy, Melanoma mortality, Immune Checkpoint Inhibitors therapeutic use
- Abstract
Importance: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival., Objective: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials., Design, Setting, and Participants: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023., Exposures: Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab., Main Outcomes and Measures: Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR)., Results: A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69)., Conclusions and Relevance: This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.
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- 2024
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28. Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients.
- Author
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Rauwerdink DJW, Not OV, de Meza M, Doorn RV, Hage JV, Eertwegh AJMVD, Haanen JB, Aarts MJB, Berkmortel FWPJVD, Blank CU, Boers-Sonderen MJ, Groot JWB, Hospers GAP, Piersma D, van Rijn RS, Stevense-den Boer AM, Veldt AAMV, Vreugdenhil G, Wouters MWJM, Suijkerbuijk KPM, and Kapiteijn E
- Abstract
Introduction : The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods : This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results : A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group ( p < 0.01), and had a better ECOG performance status ( p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% ( p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% ( p < 0.01). Conclusions : Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.
- Published
- 2024
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