المؤلفون: Annegien Broeks, Michel W J M Wouters, Georgina V Long, Richard A Scolyer, Christian U Blank, Judith M Versluis, Karijn P M Suijkerbuijk, Petros Dimitriadis, Joyce Sanders, James S Wilmott, Alexander Maxwell Menzies, Yvonne M Schrage, Stephanie A Blankenstein, Robert Elens, Willeke A M Blokx, Winan van Houdt, Alexander C J van Akkooi

المصدر: Journal for ImmunoTherapy of Cancer, Vol 12, Iss 4 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses to identify prognostic and predictive biomarkers.Patients and methods Two cohorts of patients with macroscopic stage III melanoma from an ongoing biobank study were included. Clinical data were compared between an observation cohort (cohort 1) and an adjuvant intention cohort (cohort 2). RNA sequencing for translational analyses was performed and treatment subgroups (cohort 1A and cohort 2A) were compared for possible biomarkers, using a cut-off based on the treatment-naïve patients. In addition, two validation cohorts (Melanoma Institute Australia (MIA) and University Medical Centre Utrecht (UMCU)) were obtained.Results After a median follow-up of 26 months of the 98 patients in our discovery set, median recurrence-free survival (RFS) was significantly longer for the adjuvant intention cohort (cohort 2, n=49) versus the observation cohort (cohort 1, n=49). Median overall survival was not reached for either cohort, nor significantly different. In observation cohort 1A (n=24), RFS was significantly longer for patients with high interferon-gamma (IFNγ) score (p=0.002); for adjuvant patients of cohort 2A (n=24), a similar trend was observed (p=0.086). Patients with high B cell score had a longer RFS in cohort 1A, but no difference was seen in cohort 2A. The B cell score based on RNA correlated with CD20+ cells in tumor area but was not independent from the IFNγ score. In the MIA validation cohort (n=44), longer RFS was observed for patients with high IFNγ score compared with low IFNγ score (p=0.046), no difference in RFS was observed according to the B cell score. In both the observation (n=11) and the adjuvant (n=11) UMCU validation cohorts, no difference in RFS was seen for IFNγ and B cell.Conclusions IFNγ has shown to be a prognostic marker in both patients who were and were not treated with adjuvant therapy. B cell score was prognostic but did not improve accuracy over IFNγ. Our study confirmed RFS benefit of adjuvant anti-PD-1 for patients with macroscopic stage III melanoma.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/12/4/e008125.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/e0b90991b4304091afe1ffd233fc064cTest

المؤلفون: Annegien Broeks, Sofie Wilgenhof, John B A G Haanen, Karolina Sikorska, Christian U Blank, Judith M Versluis, Jan Willem B de Groot, Esmee P Hoefsmit, Elisa A Rozeman, Petros Dimitriadis, Aysegul Sari, Daan van den Broek, Disha Rao, Ruben Lacroix, Lindsay G Grijpink-Ongering, Marta Lopez-Yurda, Birthe C Heeres, Bart A van de Wiel, Claudie Flohil, Stijn W T P J Heijmink, Marieke A Vollebergh, Johannes V van Thienen

المصدر: Journal for ImmunoTherapy of Cancer, Vol 11, Iss 7 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Continuous combination of MAPK pathway inhibition (MAPKi) and anti-programmed death-(ligand) 1 (PD-(L)1) showed high response rates, but only limited improvement in progression-free survival (PFS) at the cost of a high frequency of treatment-related adverse events (TRAE) in patients with BRAFV600-mutated melanoma. Short‐term MAPKi induces T-cell infiltration in patients and is synergistic with anti-programmed death-1 (PD‐1) in a preclinical melanoma mouse model. The aim of this phase 2b trial was to identify an optimal regimen of short-term MAPKi with dabrafenib plus trametinib in combination with pembrolizumab.Methods Patients with treatment-naïve BRAFV600E/K-mutant advanced melanoma started pembrolizumab 200 mg every 3 weeks. In week 6, patients were randomized to continue pembrolizumab only (cohort 1), or to receive, in addition, intermittent dabrafenib 150 mg two times per day plus trametinib 2 mg one time per day for two cycles of 1 week (cohort 2), two cycles of 2 weeks (cohort 3), or continuously for 6 weeks (cohort 4). All cohorts continued pembrolizumab for up to 2 years. Primary endpoints were safety and treatment-adherence. Secondary endpoints were objective response rate (ORR) at week 6, 12, 18 and PFS.Results Between June 2016 and August 2018, 33 patients with advanced melanoma have been included and 32 were randomized. Grade 3–4 TRAE were observed in 12%, 12%, 50%, and 63% of patients in cohort 1, 2, 3, and 4, respectively. All planned targeted therapy was given in 88%, 63%, and 38% of patients in cohort 2, 3, and 4. ORR at week 6, 12, and 18 were 38%, 63%, and 63% in cohort 1; 25%, 63%, and 75% in cohort 2; 25%, 50%, and 75% in cohort 3; and 0%, 63%, and 50% in cohort 4. After a median follow-up of 43.5 months, median PFS was 10.6 months for pembrolizumab monotherapy and not reached for patients treated with pembrolizumab and intermittent dabrafenib and trametinib (p=0.17). The 2-year and 3-year landmark PFS were both 25% for cohort 1, both 63% for cohort 2, 50% and 38% for cohort 3 and 75% and 60% for cohort 4.Conclusions The combination of pembrolizumab plus intermittent dabrafenib and trametinib seems more feasible and tolerable than continuous triple therapy. The efficacy is promising and appears to be favorable over pembrolizumab monotherapy.Trial registration number NCT02625337.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/11/7/e006821.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/85f4bb454d4548b7b0eddc4aff9da5e2Test

المؤلفون: Leonie Müller-Jensen, Sarah Zierold, Judith M Versluis, Wolfgang Boehmerle, Petra Huehnchen, Matthias Endres, Raphael Mohr, Annette Compter, Christian U Blank, Tim Hagenacker, Friedegund Meier, Lydia Reinhardt, Anja Gesierich, Martin Salzmann, Jessica C Hassel, Selma Ugurel, Lisa Zimmer, Patricia Banks, Lavinia Spain, Jennifer A Soon, Tomohiro Enokida, Makoto Tahara, Katharina C Kähler, Ruth Seggewiss-Bernhardt, Catriona Harvey, Georgina V Long, Florian Schöberl, Louisa von Baumgarten, Thomas Hundsberger, Max Schlaak, Lars E French, Samuel Knauss, Lucie M Heinzerling

المصدر: Data in Brief, Vol 45, Iss , Pp 108649- (2022)

مصطلحات موضوعية: Immunotherapy, Cancer, Immune related adverse events, Neurotoxicity, Encephalitis, Anti-LGI1 encephalitis, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390

الوصف: Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited.We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis – two alternative causes of encephalitis – to increase the awareness of ICI-iE and improve its diagnosis and management.To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients’ medical records and compared between the groups.The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders – ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis – are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S235234092200854XTest; https://doaj.org/toc/2352-3409Test

الوصول الحر: https://doaj.org/article/c91a9542a832459593f5a6f29e793e54Test

المؤلفون: Bart Neyns, Lisa Zimmer, Caroline Robert, Celeste Lebbe, Olivier Michielin, Omid Hamid, Anne Zaremba, Oliver Klein, Ruth Plummer, Joanna Mangana, Paolo A Ascierto, Katharina C Kähler, Georgina V Long, Ryan Sullivan, Grant A McArthur, Michael Weichenthal, Egle Ramelyte, Meghan J Mooradian, Douglas B Johnson, Alexander Shoushtari, Christian U Blank, Judith M Versluis, Prachi Bhave, Claudia Trojanello, Lu Si, Inderjit Mehmi, Tasnia Ahmed, Alexander M Menzies, Adnan Khattak, Severine Roy, Matteo S Carlino, Paul C Lorigan, Clara Allayous, Rachel Roberts-Thomson, Florentia Dimitriou, Kathleen Batty, Thierry Lesimple, Serigne N Lo, Alexandre Wicky, Richard Heywood, Lena Tran, Anna Stansfeld, Julia K Schwarze, Andrea Maurichi, Hui-Ling Yeoh, Mario Santinami, Andrew M Haydon

المصدر: Journal for ImmunoTherapy of Cancer, Vol 10, Iss 7 (2022)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site.Methods Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS).Results In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites.Conclusion While the ORR to anti-PD-1/ipilimumab was significantly higher than anti-PD-1 and PFS numerically higher, in this retrospective cohort this benefit did not translate to improved OS. Future trials should specifically include patients with acral melanoma, to help determine the optimal management of this important melanoma subtype.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/10/7/e004668.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/0b1c2b670e1e4ec1b95b97b6b085c47bTest

المؤلفون: Lisa Zimmer, Serigne Lo, Caroline Robert, John Haanen, Ines Pires da Silva, Reinhard Dummer, Michael Manos, Joanna Mangana, Marcus O Butler, Richard D Carvajal, Alon Vaisman, Christian Posch, F Stephen Hodi, Paola Queirolo, Axel Hauschild, Christian U Blank, Maria Grazia Vitale, Karijn P M Suijkerbuijk, Alexander M Menzies, Aljosja Rogiers, Chiara Tentori, Joseph M Grimes, Megan H Trager, Sharon Nahm, Peter Bowling, Neha Papneja, April A N Rose, Jessica S W Borgers, Severine Roy, Thiago Pimentel Muniz, Tim Cooksley, Jeremy Lupu, Samuel D Saibil, Michael Erdmann, Laura Pala, Ryan J Sullivan, Wilson H Miller Jr, Osama E Rahma, Paul C Lorigan

المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 1 (2021)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/9/1/e000908corr1.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/a11788d6e7784eafb0cbc66b79d31b22Test

المؤلفون: Dirk Schadendorf, Carola Berking, Lisa Zimmer, Serigne Lo, Caroline Robert, John Haanen, Ines Pires da Silva, Paolo Antonio Ascierto, Reinhard Dummer, Michael Manos, Joanna Mangana, Marcus O Butler, Richard D Carvajal, Georgina V Long, Alon Vaisman, Christian Posch, F Stephen Hodi, Paola Queirolo, Axel Hauschild, Christian U Blank, Maria Grazia Vitale, Carlo Alberto Tondini, Leyre Zubiri, Arielle Elkrief, Karijn P M Suijkerbuijk, Mario Mandala, Alexander M Menzies, Aljosja Rogiers, Chiara Tentori, Joseph M Grimes, Megan H Trager, Sharon Nahm, Peter Bowling, Neha Papneja, April A N Rose, Jessica S W Borgers, Severine Roy, Thiago Pimentel Muniz, Tim Cooksley, Jeremy Lupu, Samuel D Saibil, Matteo S Carlino, Michael Erdmann, Laura Pala, Ryan J Sullivan, Wilson H Miller Jr, Kerry L Reynolds, Osama E Rahma, Paul C Lorigan

المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 1 (2021)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Patients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer.Methods We analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality.Findings Thirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off.Interpretation COVID-19–related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/9/1/e001931.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/0880e80bb8394806afbc90b0e9140059Test

المؤلفون: Anne M May, Michel W J M Wouters, Ellen Kapiteijn, John B A G Haanen, Christian U Blank, Maureen J B Aarts, Rik J Verheijden, Astrid A M van der Veldt, Marye J Boers-Sonderen, Franchette W P J van den Berkmortel, Alfonsus J M van den Eertwegh, Jan Willem B de Groot, Jacobus J M van der Hoeven, Geke A P Hospers, Djura Piersma, Rozemarijn S van Rijn, Albert J ten Tije, Gerard Vreugdenhil, Michiel C T van Zeijl, Karijn P M Suijkerbuijk

المصدر: ESMO Open, Vol 5, Iss 6 (2020)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Immune checkpoint inhibitor (ICI) can cause severe and sometimes fatal immune-related adverse events (irAEs). Since these irAEs mimick immunological disease, a female predominance has been speculated on. Nevertheless, no demographic or tumour-related factors associated with an increased risk of irAEs have been identified until now.Methods Risk ratios of severe (grade ≥3) irAEs for age, sex, WHO performance status, number of comorbidities, stage of disease, number of metastases and serum lactate dehydrogenases (LDH) were estimated using data from anti-PD1-treated patients with advanced melanoma in the prospective nationwide Dutch Melanoma Treatment Registry.Results 111 (11%) out of 819 anti-programmed cell death 1 treated patients experienced severe irAEs. Patients with non-lung visceral metastases (stage IV M1c or higher) less often experienced severe irAEs (11%) compared with patients with only lung and/or lymph node/soft tissue involvement (stage IV M1b or lower; 19%; adjusted risk ratio (RRadj) 0.63; 95% CI 0.41 to 0.94). Patients with LDH of more than two times upper limit of normal had a non-significantly lower risk of developing severe irAEs than those with normal LDH (RRadj 0.65; 95% CI 0.20 to 2.13). None of the other variables were associated with severe irAEs.Conclusion In patients with melanoma, more advanced disease is associated with a lower rate of severe irAEs. No association with sex was found.

وصف الملف: electronic resource

العلاقة: https://esmoopen.bmj.com/content/5/6/e000945.fullTest; https://doaj.org/toc/2059-7029Test

الوصول الحر: https://doaj.org/article/e9745cefbc3341ff89aba01c2bbe198fTest

المؤلفون: Olivier J. van Not, Thijs T. Wind, Rawa K. Ismail, Arkajyoti Bhattacharya, Mathilde Jalving, Christian U. Blank, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Marye J. Boers-Sonderen, Alfonsus J. M. van den Eertwegh, Jan Willem B. de Groot, John B. Haanen, Ellen Kapiteijn, Manja Bloem, Djura Piersma, Rozemarijn S. van Rijn, Marion Stevense-den Boer, Astrid A. M. van der Veldt, Gerard Vreugdenhil, Michel W. J. M. Wouters, Willeke A. M. Blokx, Karijn P. M. Suijkerbuijk, Rudolf S. N. Fehrmann, Geke A. P. Hospers

المصدر: Cancers; Volume 15; Issue 11; Pages: 2922

مصطلحات موضوعية: advanced melanoma, immunotherapy, brain metastases, survival tree

الوصف: The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.

وصف الملف: application/pdf

العلاقة: Cancer Immunology and Immunotherapy; https://dx.doi.org/10.3390/cancers15112922Test

الإتاحة: https://doi.org/10.3390/cancers15112922Test

المؤلفون: Florine L. Boer, Vincent K. Y. Ho, Marieke W. J. Louwman, Anne M. R. Schrader, Charlotte L. Zuur, Christian U. Blank, Mariette I. E. van Poelgeest, Ellen H. W. Kapiteijn

المصدر: Cancers; Volume 15; Issue 5; Pages: 1541

مصطلحات موضوعية: mucosal melanoma, incidence, survival, immune and targeted therapy

الوصف: Background: Mucosal melanoma (MM) is a rare tumour with a poor prognosis. Over the years, immune and targeted therapy have become available and have improved overall survival (OS) for patients with advanced cutaneous melanoma (CM). This study aimed to assess trends in the incidence and survival of MM in the Netherlands against the background of new effective treatments that became available for advanced melanoma. Methods: We obtained information on patients diagnosed with MM during 1990–2019 from the Netherlands Cancer Registry. The age-standardized incidence rate and estimated annual percentage change (EAPC) were calculated over the total study period. OS was calculated using the Kaplan–Meier method. Independent predictors for OS were assessed by applying multivariable Cox proportional hazards regression models. Results: In total, 1496 patients were diagnosed with MM during 1990–2019, mostly in the female genital tract (43%) and the head and neck region (34%). The majority presented with local or locally advanced disease (66%). The incidence remained stable over time (EAPC 3.0%, p = 0.4). The 5-year OS was 24% (95%CI: 21.6–26.0%) with a median OS of 1.7 years (95%CI: 1.6–1.8). Age ≥ 70 years at diagnosis, higher stage at diagnosis, and respiratory tract location were independent predictors for worse OS. Diagnosis in the period 2014–2019, MM located in the female genital tract, and treatment with immune or targeted therapy were independent predictors for better OS. Conclusion: Since the introduction of immune and targeted therapies, OS has improved for patients with MM. However, the prognosis of MM patients is still lower compared to CM, and the median OS of patients treated with immune and targeted therapies remains fairly short. Further studies are needed to improve outcomes for patients with MM.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/cancers15051541Test

الإتاحة: https://doi.org/10.3390/cancers15051541Test

المؤلفون: Melissa M. De Meza, Willeke A. M. Blokx, Johannes J. Bonenkamp, Christian U. Blank, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Marye J. Boers-Sonderen, Jan Willem B. De Groot, John B. A. G. Haanen, Geke A. P. Hospers, Ellen Kapiteijn, Olivier J. Van Not, Djura Piersma, Rozemarijn S. Van Rijn, Marion Stevense-den Boer, Astrid A. M. Van der Veldt, Gerard Vreugdenhil, Alfonsus J. M. Van den Eertwegh, Karijn P. M. Suijkerbuijk, Michel W. J. M. Wouters

المصدر: Cancers; Volume 15; Issue 2; Pages: 409

مصطلحات موضوعية: melanoma, adjuvant therapy, targeted therapy, immune checkpoint inhibition

الوصف: Adjuvant BRAF/MEK- and anti-PD-1 inhibition have significantly improved recurrence-free survival (RFS) compared to placebo in resected stage III BRAF-mutant melanoma. However, data beyond the clinical trial setting are limited. This study describes the toxicity and survival of patients treated with adjuvant BRAF/MEK inhibitors and compares outcomes to adjuvant anti-PD-1. For this study, stage III BRAF V600 mutant cutaneous melanoma patients treated with adjuvant BRAF/MEK-inhibition or anti-PD-1 were identified from the Dutch Melanoma Treatment Registry. BRAF/MEK- and anti-PD-1-treated patients were matched based on propensity scores, and RFS at 12 and 18 months were estimated. Between 1 July 2018 and 31 December 2021, 717 patients were identified. Of these, 114 patients with complete records were treated with BRAF/MEK therapy and 532 with anti-PD-1. Comorbidities (p = 0.04) and geographical region (p < 0.01) were associated with treatment choice. In 45.6% of BRAF/MEK-treated patients, treatment was prematurely discontinued. Grade ≥ 3 toxicity occurred in 11.5% of patients and was the most common cause of early discontinuation (71.1%). At 12 and 18 months, RFS in BRAF/MEK-treated patients was 85% and 70%, compared to 68% and 68% in matched anti-PD-1-treated patients (p = 0.03). In conclusion, comorbidities and geographical region determine the choice of adjuvant treatment in patients with resected stage III BRAF-mutant melanoma. With the currently limited follow-up, BRAF/MEK-treated patients have better RFS at 12 months than matched anti-PD-1-treated patients, but this difference is no longer observed at 18 months. Therefore, longer follow-up data are necessary to estimate long-term effectiveness.

وصف الملف: application/pdf

العلاقة: Cancer Immunology and Immunotherapy; https://dx.doi.org/10.3390/cancers15020409Test

الإتاحة: https://doi.org/10.3390/cancers15020409Test