EJC Skin Cancer最新文献

{"title":"Efficacy of combined BRAF-MEK inhibitor second-line therapy in patients with non-resectable or metastatic BRAFV600-positive melanoma after prior immunotherapy: A retrospective EUMelaReg multicenter study","authors":"Eva Ellebaek ,&nbsp;Michael Weichenthal ,&nbsp;Iva Gavrilova ,&nbsp;Nethanel Asher ,&nbsp;Patrick Terheyden ,&nbsp;Jochen Utikal ,&nbsp;Amina Jalovčić Suljeviić ,&nbsp;Claudia Pföhler ,&nbsp;Igor Stojkovski ,&nbsp;Rudolf Alexander Herbst ,&nbsp;Selma Ugurel ,&nbsp;Christina Ruhlmann ,&nbsp;Alfonso Berrocal ,&nbsp;Margarita Majem ,&nbsp;Branko Dujovic ,&nbsp;Viktor Šabarić ,&nbsp;Tomislav Duvancic ,&nbsp;Ainara Soria ,&nbsp;Marco Donia ,&nbsp;Henrik Schmidt ,&nbsp;Dirk Schadendorf","doi":"10.1016/j.ejcskn.2025.100773","DOIUrl":"10.1016/j.ejcskn.2025.100773","url":null,"abstract":"<div><h3>Background</h3><div>Randomised trials recently showed that sequencing of first-line (1 L) immune checkpoint inhibitor (ICI) and second-line (2 L) BRAF-MEK-inhibitor (BRAF/MEKi) combination therapy provides better clinical outcomes in <em>BRAF</em>^{<em>V600</em>}-mutated, irresectable/metastatic melanoma than the inverse sequence. However, efficacy benchmark data for 2 L BRAF/MEKi are limited as the combination was developed for 1 L use, lacking estimates for the impact of prior ICI.</div></div><div><h3>Methods</h3><div>This retrospectively study analysed 2343 patients from the EUMelaReg registry with <em>BRAF</em>^{<em>V600</em>}-mutated melanoma who received BRAF/MEKi either as 2 L after failing 1 L ICI (n = 654) or as 1 L treatment (n = 1689). Patients with prior adjuvant ICI or BRAF/MEKi were excluded. Prognostic imbalances between the two groups were adjusted using 1:1 inverse propensity score matching. Key efficacy outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and time on treatment (TOT).</div></div><div><h3>Results</h3><div>Patients in the 2 L cohort achieved outcomes from start of treatment at least equivalent to the matched 1 L BRAF/MEKi cohort. Kaplan-Meier estimates demonstrated longer median PFS (8.4 vs 7.7 months; p = 0.01) and longer median TOT (7.8 vs 6.2 months; p = 0.002) for patients treated with 2 L BRAF/MEKi compared to 1 L. Median OS from start of 2 L (17.2 months) or 1 L (16.0 months) BRAF/MEKi was similar (p = 0.73) despite inherent bias from differing index dates. ORR among both groups (56.4 % vs 53.5 %; p = 0.32) was equal.</div></div><div><h3>Conclusion</h3><div>This study further supports the recommended sequencing of ICI as 1 L and BRAF/MEKi as 2 L therapy for patients with <em>BRAF</em>^{<em>V600</em>}-mutated melanoma. It shows that prior failure of ICI does not compromise the efficacy of BRAF/MEKi treatment.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100773"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAF/MEK inhibitor rechallenge in patients with non-resectable or metastatic BRAF V600-mutated melanoma: A stratified, controlled, retrospective EUMelaReg multicenter study","authors":"Michael Weichenthal ,&nbsp;Iva Gavrilova ,&nbsp;Peter Mohr ,&nbsp;Berna C. Özdemir ,&nbsp;Nethanel Asher ,&nbsp;Eva Ellebaek ,&nbsp;Jens Ulrich ,&nbsp;Alexander Kreuter ,&nbsp;Aleksander Popovic ,&nbsp;Christina Ruhlmann ,&nbsp;Igor Stojkovski ,&nbsp;Shaked Lev-Ari ,&nbsp;Edgar Dippel ,&nbsp;Almudena García Castaño ,&nbsp;Lorena Bellido Hernández ,&nbsp;Henrik Schmidt ,&nbsp;Egle Ramelyte ,&nbsp;Dimitrios Ziogas ,&nbsp;Luisa Piccin ,&nbsp;Katarzyna Kozak ,&nbsp;Dirk Schadendorf","doi":"10.1016/j.ejcskn.2026.100776","DOIUrl":"10.1016/j.ejcskn.2026.100776","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic options for BRAF^V600-mutant melanoma in patients who progress on BRAF/MEK-inhibitors (BRAF/MEKi) and immune-checkpoint-inhibitor (ICI) therapy, are limited. We conducted a retrospective registry study to investigate post-ICI rechallenge with BRAF/MEKi, stratified by type of initial BRAF/MEKi therapy.</div></div><div><h3>Methods</h3><div>This retrospective study analysed patients from the EUMelaReg registry, who received adjuvant or first-line (1 L) BRAF/MEKi in the advanced setting, followed by ICI therapy and were later retreated with BRAF/MEKi. Overall response rate (ORR) for rechallenge served as primary endpoint, disease-control rate (DCR), progression-free survival (PFS), and overall survival (OS) were further endpoints. A covariate-matched control group of patients who received BRAF/MEKi only after 1 L ICI failure was selected for comparison.</div></div><div><h3>Results</h3><div>Among patients previously treated with adjuvant (n = 42) or non-adjuvant (n = 142) BRAF/MEKi, rechallenge after one interim ICI line resulted in ORRs of 26.2 % and 30.3 % and DCRs of 42.9 % and 61.8 %, respectively. Median PFS was 8.4 and 5.1 months, median OS 13.8 and 8.6 months, respectively. Overall, the rechallenge group had a 1-year OS of 43.2 %, lower than the matched control (58.9 %). The adjuvant subgroup was similar to control (55.4 %), while the advanced subgroup showed notably poorer survival (39.9 %). Subgroup analyses showed that both the pre-ICI response to BRAF/MEKi treatment and progressive disease prior to ICI were associated with outcome of the BRAF/MEKi rechallenge.</div></div><div><h3>Conclusion</h3><div>Rechallenge with BRAF/MEKi therapy under real-world conditions for advanced melanoma provides a valid treatment option. For patients who received their initial BRAF/MEKi therapy as adjuvant therapy there seems to be only limited impairment of outcomes.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100776"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exceptional case of tumor lysis syndrome following Encorafénib-Binimétinib therapy for metastatic melanoma","authors":"Adielle Abecassis ,&nbsp;Laura Perray ,&nbsp;Rafaele Molinier ,&nbsp;Safa Idoudi ,&nbsp;Helene Kemp ,&nbsp;Céleste Lebbé ,&nbsp;Laetitia Vercellino ,&nbsp;Emilien Ezine ,&nbsp;Marie Fournier","doi":"10.1016/j.ejcskn.2026.100775","DOIUrl":"10.1016/j.ejcskn.2026.100775","url":null,"abstract":"<div><div>We report a case of tumor lysis syndrome (TLS) occurring 48 h after initiation of targeted therapy with Encorafénib and Binimétinib in a patient with an extensive metastatic melanoma harboring a BRAF V600E mutation. The patient required intensive care management, including systemic treatment with an antihyperuricemic agent and hemodialysis. Targeted therapy with Dabrafénib and Tramétinib was successfully reintroduced fifteen days later without TLS recurrence. TLS is a rare complication in melanoma, more commonly associated with targeted therapy or combined immunotherapy. Close monitoring is recommended in patients with high tumor burden when initiating these treatments.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100775"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes of cutaneous basal cell and squamous cell carcinomas with < 1 mm close primary surgical excision margins managed in a UK tertiary centre multidisciplinary team","authors":"Benjamin Clay ,&nbsp;Robert Manton ,&nbsp;John Kiely ,&nbsp;Animesh Patel ,&nbsp;Amit Roshan","doi":"10.1016/j.ejcskn.2026.100774","DOIUrl":"10.1016/j.ejcskn.2026.100774","url":null,"abstract":"<div><h3>Background</h3><div>Cutaneous basal cell and squamous cell carcinomas are primarily treated with surgical excision. UK guidelines designate histopathological margins of R0 + ≥1 mm as “clear”, R0 + &lt;1 mm as “close” and R1 as “involved”. Close/involved margins confer “high-risk” status, mandating multi-disciplinary team review for consideration of further intervention. We aimed to elucidate long-term outcomes of BCCs and SCCs with close and/or involved margins at primary excision compared to clear margins.</div></div><div><h3>Methods</h3><div>694 BCCs and 296 SCCs, median follow-up 3 and 16 months, respectively, at a UK University Hospital. All lesions excised with predetermined margins and subsequent management guided by MDT. Survival analysis and multiple logistic regression employed to study outcomes by margin status at excision.</div></div><div><h3>Results</h3><div>In 694 BCCs, 539 (77.7 %) were clear at both deep and peripheral margins, 127 (18.3 %) had a single close/involved margin, and 28 (4.0 %) were close/involved at both margins. Of BCCs with close/involved margin(s), 123/155 (79.3 %) had no further intervention. BCCs with a single close/involved margin had no increased risk of local recurrence compared to lesions with clear margins (HR 1.23,95 %CI [0.41–3.72]). In 296 SCCs, 208 (70.3 %) were clear at both margins, 63 (21.3 %) had close margin(s), and 25 (8.4 %) had involved margin(s). Of SCCs with close margin(s), 43/88 (48.8 %) had no further intervention. Lesions with close margin(s) had no increased risk of local recurrence compared to lesions with clear margins (HR 1.39,95 % CI [0.49–3.94]).</div></div><div><h3>Conclusions</h3><div>BCCs and SCCs with low tumour burden at the margins managed by MDT have long-term recurrence risk similar to lesions with clear margins.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100774"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switch to every-other-day sonidegib dose reduction schedule in advanced basal cell carcinoma: a multicenter retrospective observational study on effectiveness and safety","authors":"Maria Mannino ,&nbsp;Alessandro Di Stefani ,&nbsp;Massimiliano Scalvenzi ,&nbsp;Paolo Antonio Ascierto ,&nbsp;Maria Concetta Fargnoli ,&nbsp;Vincenzo De Giorgi ,&nbsp;Giuseppe Argenziano ,&nbsp;Pietro Quaglino ,&nbsp;Francesco Lacarrubba ,&nbsp;Iris Zalaudek ,&nbsp;Emi Dika ,&nbsp;Caterina Longo ,&nbsp;Giovanni Pellacani ,&nbsp;Vincenzo Maione ,&nbsp;Paola Queirolo ,&nbsp;Luca Bianchi ,&nbsp;Enrico Bocchino ,&nbsp;Claudia Costa ,&nbsp;Alessia Villani ,&nbsp;Marco Palla ,&nbsp;Ketty Peris","doi":"10.1016/j.ejcskn.2025.100772","DOIUrl":"10.1016/j.ejcskn.2025.100772","url":null,"abstract":"<div><h3>Background</h3><div>Sonidegib displays class-specific adverse events (AEs), which impair therapeutic adherence. Every-other-day administration is within the label of sonidegib approval.</div></div><div><h3>Objective</h3><div>to investigate the effectiveness and safety profile of every-other-day sonidegib in locally advanced basal cell carcinoma (laBCC) patients after a course of once-daily sonidegib.</div></div><div><h3>Methods</h3><div>a multicenter retrospective observational study was performed at 15 Italian tertiary-referral centers (January 2016 – May 2024). Fisher’s exact and Mann-Whitney test detected differences between the cohorts. Kaplan-Meier method estimated progression free survival (PFS). Univariate and multivariate logistic regressions investigated the association with switching to the every-other-day schedule.</div></div><div><h3>Results</h3><div>165 laBCC patients were enrolled, of whom 60 switched from once-daily to every-other-day sonidegib. Median sonidegib treatment duration was 14 months (range: 1–26) in the continuous regimen cohort, and 23 months (range: 6–29) in the reduced regimen cohort, p value &lt; 0.0001. The objective response rate (ORR) was 80.8 % (95 % confidence interval [CI]: 87.4–72) and 84.8 % (95 % CI: 91.6–74.3) for patients on the once-daily and on the every-other-day sonidegib schedule, respectively. Median duration of response was 9.5 months (range: 1–37) and 6 months (range: 1–28) in the continuous and in the reduced regimen cohorts, respectively. PFS probability was reduced in the every-other-day sonidegib group compared to the once-daily group (hazard ratio: 4.8, 95 % CI: 1.10–21.27; p = 0.003). 62.6 % and 19.7 % patients experienced at least one AE on the once-daily and on the every-other-day schedule, respectively, p value &lt; 0.0001.</div></div><div><h3>Conclusion</h3><div>Switch to the every-other-day sonidegib schedule is safe and effective, albeit with reduced tumor control in the long-term.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"4 ","pages":"Article 100772"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selecting first-line immunotherapy in advanced melanoma: Current evidence on efficacy across diverse patient populations","authors":"Sophia Kreft ,&nbsp;Tommaso Bosetti ,&nbsp;Rebecca Lee ,&nbsp;Paul Lorigan","doi":"10.1016/j.ejcskn.2025.100285","DOIUrl":"10.1016/j.ejcskn.2025.100285","url":null,"abstract":"<div><div>Immunotherapy has dramatically changed the outcome for patients with advanced melanoma, with significant improvements in overall survival and potential cure for some. The recent approval of nivolumab in combination with relatlimab (nivolumab-relatlimab) added a third immunotherapy option for first-line treatment for advanced melanoma. Nivolumab-relatlimab has shown greater efficacy compared to single-agent nivolumab and has fewer unacceptable side effects compared to the combination of ipilimumab and nivolumab (ipilimumab-nivolumab). However, the lack of both long-term follow-up data and direct comparison with ipilimumab-nivolumab raises uncertainty about where to position nivolumab-relatlimab in clinical practice. Since most patients who respond to combination ipilimumab-nivolumab also respond to nivolumab-relatlimab, and many to single-agent anti-programmed death-1 (PD-1) monotherapy, the challenge is to identify the subgroup of patients who need ipilimumab-nivolumab and would not achieve similar benefits from less toxic alternatives. This review discusses the available data on efficacy of the three approved first-line immunotherapies (single-agent anti-PD-1, nivolumab-relatlimab or ipilimumab-nivolumab) and their value in distinct population groups to help guide clinical decisions.</div></div>","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143323472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved prognostic guidance with 31-gene expression profiling for patients with stage IIB-IIC cutaneous melanoma: a SEER collaboration","authors":"B. Moody ,&nbsp;B. Martin ,&nbsp;A. Hanson ,&nbsp;V. Petkov","doi":"10.1016/j.ejcskn.2025.100387","DOIUrl":"10.1016/j.ejcskn.2025.100387","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100387"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Italian interim analysis of the multinational, post-authorisation safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma: focus on time to onset of adverse events","authors":"L. Scarpato ,&nbsp;P.A. Ascierto ,&nbsp;M. Scalvenzi ,&nbsp;A. Villani ,&nbsp;P. Bossi ,&nbsp;A. Alberti ,&nbsp;V. De Giorgi ,&nbsp;L. Licitra ,&nbsp;M.C. Fargnoli ,&nbsp;P. Savoia ,&nbsp;M. Guida ,&nbsp;F. Spagnolo ,&nbsp;F. De Galitiis ,&nbsp;I. Stanganelli ,&nbsp;K. Peris","doi":"10.1016/j.ejcskn.2025.100335","DOIUrl":"10.1016/j.ejcskn.2025.100335","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100335"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metatypical Metastatic Basal Cell Carcinoma Treated with Vismodegib: Report of Two Cases","authors":"D. Amarillo,&nbsp;V. Lemes,&nbsp;G. Krygier","doi":"10.1016/j.ejcskn.2025.100322","DOIUrl":"10.1016/j.ejcskn.2025.100322","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100322"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the common mutational landscape in cutaneous melanoma and pancreatic cancer","authors":"F. Venturi ,&nbsp;E. Broseghini ,&nbsp;M. Ferracin ,&nbsp;E. Dika","doi":"10.1016/j.ejcskn.2025.100351","DOIUrl":"10.1016/j.ejcskn.2025.100351","url":null,"abstract":"","PeriodicalId":100396,"journal":{"name":"EJC Skin Cancer","volume":"3 ","pages":"Article 100351"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}