Quality of abstracts in 3 clinical dermatology journals

Background Structured abstracts have been widely adopted in medical journals, with little demonstration of their superiority over unstructured abstracts.Objectives: To compare abstract quality among 3 clinical dermatology journals and to compare the quality of structured and unstructured abstracts within those journals. Design and Data Sources: Abstracts of a random sample of clinical studies (case reports, case series, and reviews excluded) published in 2000 in the Archives of Dermatology, The British Journal of Dermatology, and the Journal of the American Academy of Dermatology were evaluated. Each abstract was rated by 2 independent investigators, using a 30-item quality scale divided into 8 categories (objective, design, setting, subjects, intervention, measurement of variables, results, and conclusions). Items applicable to the study and present in the main text of the article were rated as being present or absent from the abstract. A global quality score (range, 0-1) for each abstract was established by calculating the proportion of criteria among the eligible criteria that was rated as being present. A score was also calculated for each category. Interrater agreement was assessed with a {kappa} statistic. Mean ± SD scores were compared among journals and between formats (structured vs unstructured) using analysis of variance. Main Outcome Measures: Mean quality scores of abstracts by journal and by format. Results: Interrater agreement was good ({kappa} = 0.71). Mean ± SD quality scores of abstracts were significantly different among journals (Archives of Dermatology, 0.78 ± 0.07; The British Journal of Dermatology, 0.67 ± 0.17; and Journal of the American Academy of Dermatology, 0.64 ± 0.15; P = .045) and between formats (structured, 0.71 ± 0.11; and unstructured, 0.56 ± 0.18; P = .002). The setting category had the lowest scores. Conclusions: The quality of abstracts differed across the 3 tested journals. Unstructured abstracts were demonstrated to be of lower quality compared with structured abstracts and may account for the differences in quality scores among the journals. The structured format should be more widely adopted in dermatology journals

545 A phase 2 study of retifanlimab in patients with advanced or metastatic merkel cell carcinoma (MCC) (POD1UM-201)

BackgroundRetifanlimab (INCMGA00012) is a humanized, hinge-stabilized immunoglobulin G4 kappa (IgG4κ), anti-programmed cell death protein (PD)-1 monoclonal antibody with safety and clinical pharmacology that are characteristic for the class. Evaluation of retifanlimab in solid tumors is under investigation in phase 2 and 3 studies. POD1UM-201 is an open-label, single-arm, multicenter, phase 2 study evaluating the efficacy and safety of retifanlimab in patients with chemotherapy-naïve or chemotherapy-refractory advanced/metastatic Merkel cell carcinoma (MCC). Updated results from the chemotherapy-naïve cohort are reported here.MethodsEligible patients were ≥18 years of age, had metastatic or recurrent unresectable loco-regional MCC, Eastern Cooperative Oncology Group performance status ≤1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and had not received prior systemic treatment for MCC. Retifanlimab 500 mg IV every 4 weeks (Q4W) was administered for up to 2 years. The primary endpoint was overall response rate (ORR) assessed by independent central review per RECIST v1.1. Secondary endpoints included duration of response, disease control rate (DCR; defined as proportion of patients with either an objective response or stable disease lasting at least 6 months), progression-free survival, overall survival, safety, and pharmacokinetics.ResultsAs of April 16, 2021, 87 patients with chemotherapy-naïve advanced/metastatic MCC had received retifanlimab. Per protocol, the primary efficacy analyses are based on the first 65 patients assessed. At the data cutoff, 34 of these 65 patients (52.3%) were on treatment; 4 (6.2%) had completed treatment; and 27 (41.5%) had discontinued treatment for reasons including disease progression (18 [27.7%]), adverse event (AE; 7 [10.8%]), death (1 [1.5%]), and physician decision (1 [1.5%]). The ORR in these patients was 46.2% (n=30: complete response, 8 [12.3%]; partial response, 22 [33.8%]). The DCR was 53.8% (n=35). Other secondary efficacy results are not yet mature. Among all treated patients (n=87), 66 (75.9%) had a treatment-emergent AE (TEAE), 25 (28.7%) had a grade ≥3 TEAE, and 12 (13.8%) had a grade ≥3 treatment-related AE. Twenty-three patients (26.4%) had an immune-related AE (irAE), and 8 (9.2%) had a grade ≥3 irAE. Four patients (4.6%) discontinued treatment due to irAEs (peripheral sensorimotor neuropathy, pancreatitis, eosinophilic fasciitis, and polyarthritis [each n=1]). One patient (1.1%) had a grade 3 infusion reaction.ConclusionsThese data from the POD1UM-201 trial show that retifanlimab monotherapy at 500 mg Q4W continues to demonstrate promising clinical activity and safety in patients with advanced/metastatic chemotherapy-naïve MCC. Updated results will be presented at the meeting.AcknowledgementsThe study is sponsored by Incyte Corporation (Wilmington, DE). Statistical support was provided by Xiaohan Xu of Incyte Corporation. Editorial assistance was provided by Matthew Bidgood of Envision Pharma Group (Philadelphia, PA, USA).Trial RegistrationClinicaltrials.gov NCT03599713; EudraCT 2018-001627-39Ethics ApprovalThe study was approved by institutional review boards or independent ethics committees in Canada (McGill University Health Center-Research Ethics Board [MP-37-2019-5103, MEO-37-2019-1616]; Ontario Cancer Research Ethics Board [1728]; Health Research Ethics Board of Alberta – Cancer Committee [HREBA.CC-19-0004, HREBA.CC-19-0020]); Czech Republic (Eticka komise Fakultni nemocnice Kralovske Vinohrady, Eticka komise IKEM a FTNsP, Eticka komise Nemocnice Na Bulovce, Statni ustav pro kontrolu leciv, Eticka komise FN a LF UP Olomouc [169/18MEK24, LEK/04/07/2018, (L-18-85) 8522/23.3.2021, 22.3.2021/9965/EK-Z]); France (Comité de Protection des Personnes Ile de France X [CNRIPH : 18.11.19.49212/Id. 2043]; Agence Nationale de Sécurité du Médicament et des Produits de Santé); Germany (Ethik-Kommission der Medizinischen Fakultaet der Universitaet Duisburg-Essen [18-8371-AF]; Bundesamt fuer Strahlenschutz; Paul-Ehrlich Institute); Hungary (Egeszsegugyi Tudomanyos Tanacs Klinikai Farmakologiai Etikai Bizottsaga [IV/2407-0/2021-EKL, OGYÉI/11697-2/2021]; Orszagos Gyogyszereszeti es Elelmezes-egeszsegugyi Intezet); Italy (Comitato Etico IRCCS Pascale Napoli [116/21 E - 87/18]; Comitato Etico IRCCS di Candiolo [232/2021]; Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari [736/CE]; Comitato Etico Locale per la Sperim. Clin. dei Medicinali dell'Az. Osp.ra Univ.ria Senese di Siena [14107]; Comitato Etico dell'IRCCS Istituto Nazionale per la Ricerca sul Cancro di Genova [389/2018 - 24/05/2021]; Comitato etico degli IRCCS Istituto Europeo di Oncologia e Centro Cardiologico Monzino [IEO 948 - RE3065/IB Edition 7 dated 10Nov2020 (SA7)]; Comitato Etico, Fondazione IRCCS Istituto Nazionale dei Tumori, .c. Medicina Oncologica 1 – Fondazio [INT 01/19]; Comitato Etico IRCCS Istituto Oncologico Veneto di Padova [EM 109/2021]; Comitato Etico dell'IRCCS Istituto Dermopatico dell'Immacolata Ospedale Generale S. Carlo di Roma [550/7]; AIFA – Agenzia Italiana del Farmaco [0040152-01/04/2021-AIFA-AIFA_USC-P]; Comitatao Etico Policlinico di Modena [1017/2018/FARM/AOUMO - EMENDAMENTO SOSTANZIALE IB EDIZIONE 7 DEL 10/11/20 (201800162739-010) (p. 9869/21)]); Poland (Komisja Bioetyczna przy Centrum Onkologii [no. 55/2019]; Office for Registration of Medicinal Products, Medical Devices and Biocidal Products [UR/DBL/D/328/2019]); Spain (CEIC Hospital General Universitario Gregorio Marañon [280/18]; Agencia Española del Medicamento y Productos Sanitarios); Switzerland (Kantonale Ethikkommission Zürich (KEK-Zürich) [2019-00200]; Swissmedic [2019DR2035]); United Kingdom (North East – York Research Ethics Committee [248465]; Medicines and Healthcare products Regulatory Agency; Health Research Authority); United States (Copernicus Group IRB; Western Institutional Review Board [20181738, Work order number -– IQV1-18-309]; Roswell Park Cancer Institute IRB [STUDY00000802/P 75918]; Inova Institutional Review Board, Human Research Protection Program; Stanford IRB Research Compliance Office [48198]; Rush University Medical Center [18072304-IRB01]; University of Miami IRB; Mayo Clinic IRB – Rochester)

Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF/MEK inhibitors in patients with BRAF mutant metastatic melanoma

Background: Patients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF/MEK inhibitors (BRAF/MEKi). Methods: Patients with V600BRAF mutant metastatic melanoma treated with BRAF/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group. Results: Of 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF/MEKi and PD1±IPI (16 vs 4 days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 (62% vs 44%), AJCC M1C/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1±IPI (34% vs 57%). Median follow-up from PD1±IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1 vs PD1 across most subgroups except for females, those with 3 years OS (area under the curve, AUC=0.74), while ECOG PS ≥1, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67). Conclusions: IPI+PD1 and PD1 after BRAF/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy. Keywords: immunotherapy; melanoma

Management of Kaposi sarcoma after solid organ transplantation:A European retrospective study

Background: Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.Objective: To obtain an overview of clinical strategies about the current treatment of KS.Methods: We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.Results: Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.Limitations: The retrospective design of the study.Conclusion: Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.Dermatology-oncolog

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy

A Reliable Method for the Selection of Exploitable Melanoma Archival Paraffin Embedded Tissues for Transcript Biomarker Profiling

The source tissue for biomarkers mRNA expression profiling of tumors has traditionally been fresh-frozen tissue. The adaptation of formalin-fixed, paraffin-embedded (FFPE) tissues for routine mRNA profiling would however be invaluable in view of their abundance and the clinical information related to them. However, their use in the clinic remains a challenge due to the poor quality of RNA extracted from such tissues. Here, we developed a method for the selection of melanoma archival paraffin-embedded tissues that can be reliably used for transcript biomarker profiling. For that, we used qRT-PCR to conduct a comparative study in matched pairs of frozen and FFPE melanoma tissues of the expression of 25 genes involved in angiogenesis/tumor invasion and 15 housekeeping genes. A classification method was developed that can select the samples with a good frozen/FFPE correlation and identify those that should be discarded on the basis of paraffin data for four reference genes only. We propose therefore a simple and inexpensive assay which improves reliability of mRNA profiling in FFPE samples by allowing the identification and analysis of “good” samples only. This assay which can be extended to other genes would however need validation at the clinical level and on independent tumor series

Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma

Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab–dacarbazine group. Conclusions Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.

Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

APPORT DE L'ELECTROCHIMIOTHERAPIE EN DERMATOLOGIE (ETUDES DE PHASE I-II DANS LA MALADIE DE KAPOSI ET LES METASTASES CUTANEES DE MELANOME)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Bortezomib Does Not Prevent the Occurrence of Kaposi’s Sarcoma in Patients with Haematological Malignancies: Two Case Reports

Abstract is missing (Short communication