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Background: Nivolumab obtained approval in advanced melanoma (AM) with weight-adjusted dose (WAD) administration (3 mg/kg/2 weeks). In 2018, the dosage regimen was changed to flat dose (FD) administration (240 mg/2 weeks or 480 mg/4 weeks) based on a modeling study, without clinical data., Methods: AM patients have been prospectively included in the French national multicenter MelBase database since 2013. First-line patients treated with nivolumab monotherapy were included in the WAD or FD groups of this study. The primary end point was the incidence of grade ≥3 immune-related adverse events (irAEs). Secondary end points were incidence of any grade irAEs, and overall survival (OS) and progression-free survival (PFS). Inverse probability of treatment weighting was used to balance groups on their baseline characteristics., Results: Between 2015 and 2022, 348 patients were included: 160 in the WAD and 188 in the FD groups. In the FD group, 45% and 27% of patients weighed <75 kg and >85 kg, respectively. Grade ≥3 and any grade irAEs rates were 13.1% versus 11.7% (p = .8) and 63.1% versus 67.0% (p = .5) in the WAD and FD groups, respectively. After weighting, median PFS was 3.1 and 3.7 months (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.65-1.07), and median OS was 24.8 and 37.0 months (HR, 0.74; 95% CI, 0.54-1.01) in the WAD and FD groups, respectively., Conclusions: There was no difference in the incidence of severe irAEs and in median PFS between AM patients treated by WAD or FD nivolumab. The median OS between patient groups did not reach statistical significance., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration., Methods: We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021., Findings: 435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8-60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1-12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinuing or continuing ICIs at either of these timepoints. The 24-month discontinuation emulated trial results were more in favor of discontinuing than continuing treatment at that time point, with an absolute 48-month survival rate that was 10.5% higher (95% CI 4.4-18.1)., Interpretation: These results suggest that a one-year course of immunotherapy is both necessary and sufficient for patients with advanced melanoma. Prolonged treatment beyond 2 years does not appear to be beneficial in terms of survival and could even be detrimental., Funding: This work was supported by a grant from Bristol Myers Squibb, Merck Sharp Dhome, Pierre Fabre, Novartis, Sun Pharm, Regeneron, Sanofi, Nektar, Therapeutics and Oncyte., Competing Interests: LM reports advisory board and travel expenses from Bristol Myers Squibb, Merck Sharp and Dhome, Pierre Fabre, Novartis and Sun Pharm. SD reports advisory board and travel expenses from Bristol Myers Squibb and Merck Sharp, and Dhome; research fundings from Bristol Myers Squibb, Merck Sharp and Dhome, and Pierre Fabre. FBP reports financial support outside the submitted work from Bristol Myers Squibb, Merck Sharp and Dhome, Pierre Fabre and Novartis. JDQ reports advisory board from Merck Sharp and Dhome, Pierre Fabre, Novartis and Bristol Myers Squibb. CGM reports advisory board and travel expenses from Pierre Fabre, Bristol Myers Squibb and Merck Sharp and Dhome. PS reports advisory board and travel expenses from Bristol Myers Squibb, Merck Sharp and Dhome and Pierre Fabre and Novartis; consulting fees from Bristol Myers Squibb, Merck Sharp and Dhome, Pierre Fabre, Regeneron, Sanofi, Damae and Novartis. TL reports advisory board and travel expenses from Bristol Myers Squibb, Merck Sharp and Dhome, Pierre Fabre and Novartis. HM reports advisory board from Pierre Fabre, Bristol Myers Squibb, Merck Sharp and Dhome, Novartis, Regeneron and Sun Pharma; research funding from Pierre Fabre, Bristol Myers Squibb, Merck Sharp and Dhome, Novartis, Regeneron, Nektar Therapeutics, 4SC and Incyte; and research grant from Leo Pharma and Merck Sharp and Dhome. All other authors declare no completing interests., (© 2024 The Authors.)

Background: The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival and numerically, although not statistically, superior overall survival for ipilimumab + nivolumab. The objective of this study was to compare the efficacy and safety of nivolumab to ipilimumab + nivolumab as first-line treatment for metastatic melanoma in a real-world setting., Methods: Patients were prospectively included in the French Melbase cohort from 2013 to 2022. Eligible patients were those in first-line treatment for stage-IIIc or -IV melanoma, undergoing immunotherapy with nivolumab or ipilimumab + nivolumab. The primary endpoint was overall survival at 36 months. The secondary endpoints included progression-free survival at 36 months, best radiological response, and safety analyses. We conducted a propensity score using the IPTW method to overcome the various confounding factors and also a subgroup analysis (brain metastasis, LDH levels, and BRAF mutation status)., Results: A total of 406 patients were treated with nivolumab, and 416 with ipilimumab + nivolumab. Overall survival at 36 months was higher in the ipilimumab + nivolumab group (57.1%, ([95%CI 50.7-64.2]) than in the nivolumab group (46.6% [95%CI 41.6-52.1]), HR 1.4[1.1;1.8]. Progression-free survival at 36 months was significantly improved in the ipilimumab + nivolumab group (42.3%) compared to the nivolumab group (21.9%), with a HR 1.6[1.4;1.9]. The objective response rate was similar for the two groups (44%). The overall incidence of side effects was comparable (82 vs. 84%), and severe toxicity (grade ≥ 3) was more frequent, though not significantly so, in the ipilimumab + nivolumab arm (29% vs. 41%)., Conclusions: Our results are consistent with those from the Checkmate 067 study, except for the objective response rate and the incidence of toxicities, which proved to be lower in our analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group (P < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Background: The tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment., Patients and Methods: Patients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS)., Results: 973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients' characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1 st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1 st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively)., Conclusion: Our study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research., Competing Interests: SD reported receiving financial support from and is a consultant for BMS, Roche, and is employed by Sanofi with stock ownership. LM reported receiving financial support from and is a consultant for BMS, Amgen, Merck, Incyte, MSD, Roche, and Novartis. OD reported receiving financial support from and is a consultant for BMS, MSD, Pierre Fabre, Recordati, Genevrier, Kiowa Kirin, Leo Pharma, and Novartis. CA reported receiving financial support from Amgen, BMS, and Roche. J-PA reported receiving financial support from BMS and MSD. SD-R reported receiving financial support from BMS, Novartis and MSD. HM reported receiving financial support from BMS, Novartis, Pierre Fabre, Leo Pharma and MSD. CD reported receiving financial support from BMS, MSD, Pierre Fabre, and Novartis. JQ reported receiving financial support from BMS, Jansen Cilag. DL reported receiving financial support from BMS, MSD, Novartis, Leo Pharma, and Merck. EM reported receiving financial support from BMS, MSD, and Novartis. PS reported receiving financial support from BMS, MSD, Novartis, Roche, and Pierre Fabre. CL reported serving as a consultant for BMS and receiving financial support from BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer, and Incyte. LB reported receiving financial support from Novartis, Pierre Fabre, Roche, BMS, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Russo, Dalle, Dereure, Mortier, Dalac-Rat, Dutriaux, Leccia, Legoupil, Montaudié, Maubec, De Quatrebarbes, Arnault, Brocard, Saïag, Dreno, Allayous, Oriano, Lefevre, Lebbé and Boussemart.)

Background: Lentigo maligna (LM) is a melanocytic proliferation occurring on photo-exposed skin that may progress to LM melanoma. Surgery is recommended as first-line treatment. Excision margins of 5-10 mm remain, without international consensus. Several studies have shown that imiquimod, an immunomodulator, induces LM regression. This study investigated the effect of imiquimod versus placebo in neoadjuvant settings., Patients and Methods: We performed a prospective, randomized, multicentre, phase III clinical study. Patients were randomly assigned in 1:1 ratio to receive imiquimod or placebo for 4 weeks, followed by LM excision 4 weeks after the last application of imiquimod or placebo. The primary endpoint was extra-lesional excision, with a 5 mm margin from the residual pigmentation after imiquimod or vehicle. Secondary endpoints included the gain on the surface removed between the two groups; number of revision surgeries to obtain extra-lesional excisions; relapse-free time; and number of complete remissions after treatment., Results: A total of 283 patients participated in this study; 247 patients, 121 patients in the placebo group and 126 in the imiquimod group, accounted for the modified ITT population. The first extralesional extirpation was performed in 116 (92%) imiquimod patients and in 102 (84%) placebo patients; the difference was not significant (p = 0.0743). Regarding the surface of LM, imiquimod reduced the LM surface (4.6-3.1 cm 2 ) significantly (p < 0.001) more compared to the placebo (3.9-4.1 cm 2 )., Conclusion: Imiquimod reduces the lentigo maligna surface after 1 month of treatment, without a higher risk of intralesional excision and with a positive aesthetic outcome., (© 2023 European Academy of Dermatology and Venereology.)

Competing Interests: None disclosed.

Background: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet., Objectives: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis., Methods: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres., Inclusion Criteria: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available., Results: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2)., Conclusion: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied., Objective: To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP)., Methods: Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed., Results: Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type., Limitations: No record of standard diagnostic criteria of MUP used in the participating centers., Conclusions: Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies., Competing Interests: Conflicts of interest Dr Dalle received research grants by BMS and MSD, travel costs covered by BMS, spouse working for Sanofi; Dr Dereure reported a Consulting or Advisory Role with Bristol-Myers Squibb, Genevrier, Kiowa Kirin, Leo Pharma, MSD, Novartis, Pierre Fabre, and Recordati, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, Novartis, Pierre Fabre, and Recordati; Dr Saiag has received outside of this study personal fees from Bristol-Myers Squibb, MSD, Merck-Serono, Pfizer, Roche-Genentech, Pierre Fabre, and Novartis; Dr Arnault consulting for NOVARTIS, Dr Lebbé reported honoraria from Amgen, Bristol-Myers Squibb, Incyte, MSD, Novartis, Pfizer, Pierre Fabre, and Roche, reports a Consulting or Advisory Role with Amgen, Bristol-Myers Squibb, Merck Serono, MSD, Novartis, Roche, and Sanofi, is on the Speakers' Bureau for Amgen, Bristol-Myers Squibb, MSD, Novartis, and Roche, received Research Funding from Bristol-Myers Squibb, and Roche, reports travel, accommodations, and expenses from Bristol-Myers Squibb and MSD, and reports other relationship with Avantis Medical Systems; and Dr Montaudié reported a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre, received Research Funding from Leo Pharma and Novartis, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, Novartis, and Pierre Fabre., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

No epidemiological information about truncal acne is available. This study assessed the self-reported impact of truncal acne in adolescents and young adults, using an internet survey in France in 1,001 adolescents and young adults with truncal acne. Participants' mean age was 18.6 ± 4.3 years, 75.7% were females, 52.9% reported severe and 16.0% very severe truncal acne; 90.0% of participants with truncal acne also reported past or ongoing facial acne. Stress (46.3%), a diet high in lipids (33.2%), and sleeplessness (27.0%) were considered to be triggers of truncal acne; 44.7% consulted at least 1 healthcare professional and 28.1% searched the internet or social network for information about truncal acne. Of subjects with truncal acne, 68.4% thought constantly about their condition. Overall, 79.9% of the participants with severe acne vs 41.8% with mild or moderate acne: 41.8% thought about their acne all the time (p < 0.0001). Truncal acne heavily or very heavily impacted quality of life of 38.7% of participants. It impacted females significantly more than males (p < 0.0001). Significantly (p < 0.001) more females than males reported facial acne. A significant (p = 0.0067) association was observed between the severities of facial and truncal acne. The self-perceived impact of truncal acne in adolescents and young adults highlights the need for information as well as reinforced medical and psychological care.

Background: Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived., Methods: This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%)., Results: Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction)., Conclusion: Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Caroline Gaudy Marquestre has declared payment for lectures/presentations/writings from BMS and MSD, and support for attending meetings from MSD, BMS and Jansen. Aurelien Marabelle has declared support for the present manuscript from Unicancer and Gustave Roussy Institute, grants or contract from BMS, MSD and Sanofi, consulting fees from Sanofi, payment for lectures/presentations/writings from BMS and MSD, support for attending meetings from BMS and MSD, participation on Advisory Board with MSD, have leadership role in the board of the French Immune-Therapy for Cancer scholar society. Marie Beylot-Barry has declared payment for lectures/presentations/writings from Sun Pharma. Nicole Basset-Seguin has declared consulting fees from Regeneron/Sanofi and Sun Pharma, payments for lectures/presentations/writings from Regeneron/Sanofi and Sun Pharma, support for attending meetings from Regeneron/Sanofi and Sun Pharma, and have participated on Advisory Board for Regeneron/Sanofi and Sun Pharma. Philippe Saiag has declared consulting fees from BMS outside the topic of this study. Philippe Jamme has declared consulting fees from BMS, support for attending meetings from Pierre Fabre, and have participated on Advisory Board with Pierre Fabre, BMS and Novartis. Celeste Lebbe has declared support for the present manuscript from Amgen, BMS, Merck Serono, MSD, Novartis, Pierre Fabre, Roche and Sanofi; she have declared consulting fees from Amgen, BMS, MSD, Novartis and Roche; payments for lectures/presentations/writings from Amgen, BMS, MSD, Novartis, Pfizer, Pierre Fabre, Roche; payment for expert testimony form Amgen, BMS, MSD, Novartis, Roche; support for attending meetings from BMS, MSD, Novartis, Pierre Fabre, Sanofi. Laurent Mortier has provided time for consulting and participation to scientific advisory boards of the following compagnies: Sun pharma, Novartis, Pierre Fabre and MSD, and have participated in congress with the same companies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Nine drugs have been marketed for 10 years for the treatment of advanced melanoma (AM). With half of patients reaching a second line, the optimal sequence of treatments remains unclear. To inform policy-makers about their efficiency, we performed a cost-effectiveness analysis of sequential strategies in clinical practice in France, for BRAF-mutated and wild-type patients. A multistate model was developed to describe treatment sequences, associated costs, and health outcomes over 10 years. Sequences, clinical outcomes, utility scores, and economic data were extracted from the prospective Melbase cohort, collecting individual data in 1518 patients since 2013, from their AM diagnosis until their death. To adjust the differences in patients' characteristics among sequences, weighting by inverse probability was used. In the BRAF-mutated population, the MONO-targeted therapies (TT)-anti-PD1 sequence was the less expensive, whereas the anti-PD1-BI-TT sequence had an incremental cost-effectiveness ratio (ICER) of 180,441 EUR/QALY. Regarding the BRAF wild-type population, the three sequences constituted the cost-effective frontier, with ICERs ranging from 116 to 806,000 EUR/QALY. For BRAF-mutated patients, the sequence anti-PD1-BI-TT appeared to be the most efficient one in BRAF-mutated AM patients until 2018. Regarding the BRAF wild-type population until 2018, the sequence starting with IPI+NIVO appeared inefficient compared to anti-PD1, considering the extra cost for the QALY gained.

Background: Janus kinase (JAK) inhibitors are targeted therapies with a potential imunomodulatory and anti-inflammatory effect, indicated in various dysimmune pathologies. Skin cancers have been reported to occur in patients treated with JAK inhibitors. However, drug safety in clinical trials did not confirm that risk, but these studies are performed on controlled population and in a limited time of follow up., Objectives: The aim of this study is to evaluate in real life condition if a disproportionality signal exists between JAK inhibitors treatment and skin cancers., Methods: We performed cases/non cases analysis in VigiBase® (the World Health Organization international database of suspected adverse drug reaction) using information component to search for a disproportionality signal of skin cancers from JAK inhibitor. We extracted all reports of skin cancers from the French Pharmacovigilance database occurring since 1978 up to 31 st December 2019 for the three existing JAK inhibitors on market: ruxolitinib, tofacitinib and baricitinib. Only melanoma, squamous cell carcinoma and Merkel cell carcinoma were analyzed, according to the pathophysiology of these cancers and their link with immunosuppression., Results: A disproportionality signal was found positive for squamous cell carcinoma with ruxolitinib (IC025=3.92) and tofacitinib (IC025=0.82), for melanoma with ruxolitinib (IC025=0.81) and tofacitinib (IC025=0.74), and Merkel cell carcinoma with ruxolitinib (IC025=4) and tofactinib (IC025=1.01) and only for Merkel cell carcinoma with baricitinib (IC025=0.53). Moreover, Merkel cell carcinoma, a very rare skin cancer more prevalent in immunodepressed patients was particularly represented in our sample and was associated with a significant disproportionality signal with all the studied JAK inhibitors., Conclusion: Our study shows that JAK inhibitors could be associated with an extra risk to develop skin cancers. Could an anti-viral or immunovigilance disruption mechanism brought by JAK inhibitors explain an over-risk with Merkel cell carcinoma, which were notably represented in our sample? Considering pharmacovigilance method limitations, further pharmacoepidemiological studies are required to assess a causal link between JAK inhibitors treatment and skin cancers development., (Copyright © 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Mitogen-activating protein kinase inhibitors (MAPKis) are largely used in V600E/K BRAF-mutated metastatic melanomas, but data regarding effectiveness of targeted therapy in patients with rare BRAF mutations and molecular description of these infrequent mutations are scarce., Patients and Methods: A multicenter study was conducted on patients with metastatic melanoma harboring a well-identified mutation of BRAF and enrolled from March 2013 to June 2021 in the French nationwide prospective cohort MelBase. The molecular BRAF mutation pattern, response to MAPKis when applicable, and survival data were analyzed., Results: Of 856 selected patients, 51 (6%) harbored a non-V600E/K BRAF mutation involving codons V600 (24 of 51, 47%; V600G 27.4%, V600R 15.6%), K601 (6 of 51, 11.7%), and L597 (4 of 51, 7.8%). An objective response to MAPKis either BRAF inhibitor (BRAFi) alone or combined with MEK inhibitor was achieved in 56% (353 of 631) of V600E/K, 58% (11 of 19) of non-E/K V600, and 22% (2 of 9) of non-V600 BRAF-mutated patients, with a median progression-free survival of 7.7, 7.8, and 2.8 months, respectively. Overall, objective response rate was higher with BRAFi + MEK inhibitor combination than with BRAFi in monotherapy for each subset., Conclusion: Rare BRAF mutations are not anecdotal in the metastatic melanoma population. Although data interpretation must remain careful owing to the limited size of some subsets of patients, non-E/K V600 BRAF mutations seem to confer a high sensitivity to targeted therapy, whereas MAPKis seem less effective in patients with non-V600 BRAF mutations. However, this strategy may be used as an alternative option in the case of immunotherapy failure in the latter population.

Background: Skin phototype, latitude and sun exposure are classic risk factors for melanomas but are not relevant to acrolentiginous melanomas (ALM). ALM is not related to chronic sun exposure because the thick stratum corneum acts as a barrier to penetration of UV rays, whereas LMM occurs in skin with high photoaging due to chronic sun exposure., Objectives: This study aimed to determine if any difference exists between "solar" melanomas and "non-solar" melanomas based on a comparison between LMM and ALM., Materials & Methods: We extracted all data for ALM and LMM patients, from March 2012 to September 2020, from the RIC-Mel national database to perform a descriptive cohort analysis of 1,056 Caucasian cases., Conclusion: The profiles of solar-related and non-solar melanoma seem to be different, and prognostic factors of ALM at diagnosis are less favourable compared to LMM, suggesting that non-solar melanoma is more aggressive than solar-related melanoma and that sentinel lymph node biopsy should be performed.

The principal actors in acne are the sebaceous gland, keratinocytes of the follicle and skin microbiome/innate immunity. Current acne treatments are frequently accompanied by side effects or may cause antibacterial resistance. New formulations and emerging treatments with novel mechanisms of action and improved formulations have recently been made available or are currently under development. This review provides an update on the most recent advances in topical or systemic acne therapy related to recent data on the pathophysiology of acne. A review of the most recent literature about new and emerging acne treatments since 2016 listed in the PubMed and Clinicaltrials.gov database was performed by a group of dermatologists interested in acne (GEA). Several novel treatments have been made available or are currently under development, including Clascosterone, Trifarotene and Sarecy-cline, as well as more effective and better tolerated formulations of existing compounds, such as Minocycline, Tretinoin, Tazarotene and Lidose-isotretinoin, and emerging acne therapies (including hyaluronic acid, cannabidiol, modulators of the skin microbiota, insulin-like growth factor, vaccines, bacteriophages, probiotics and antimicrobial peptides), targeting the sebaceous gland and its activity, inflammation or keratinocytes of the follicle and skin microbiome including Cutibacterium acnes. Recently, in addition to other fixed combinations, a fixed combination of adapalene and benzoyl peroxide that targets acne scars has been made available for the first time. The newly available products and other potentially emerging treatment options will increase the armamentarium of acne therapies and potentially reduce its prevalence worldwide.

Introduction: Only a small amount of published data regarding truncal acne is available, and no proper tool to assess its severity exists., Aim: The aim of the study was to provide dermatologists with an easy-to-use tool to assess truncal acne (TRASS, truncal acne severity scale) using a global approach., Methods: A scoring tool that assesses the severity of acne (based on GEA and ECLA scales) on the trunk using a global approach was built, including three sub-scores: family history, clinical signs and quality of life (QoL). In order to test TRASS, the experts used photographs of 47 patients attending their clinics with truncal acne. The regression optimized (ROP) model was applied to assess the diagnosis performance of TRASS and to identify items contributing to the classification of the patients. Internal testing was made to demonstrate the robustness of the model. Correlation analyses between the different items were performed to evaluate the interaction between the different items and their impact on the severity grading of truncal acne., Results: Patients with the most severe acne were identified by TRASS. The error level was 6.6% after internal validation and 10.4% when using the median value or the centile 75th (6.6% and 10.4%). Correlation was significant between systemic treatment and scars (P = 0.0025) and nodules (P = 0.01988) and between location and QoL (P = 0.0095)., Conclusion: Truncal acne severity scale is the first global, patient-centred approach to evaluate truncal acne by scoring the importance of each factor independently from its clinical severity. TRASS may allow the practitioner to choose and validate the most suitable therapy together with the patient in order to treat his or her truncal acne successfully and to limit treatment failure., (© 2022 European Academy of Dermatology and Venereology.)

Background: Photodermatoses are sun-related inflammatory skin diseases. They usually require phototesting in diagnosis. However, fewer and fewer medical centers in France are equipped with photobiological equipment., Objectives: The main purpose was to evaluate the relevance of phototesting in photodermatosis diagnosis. The second goal was to study the proportions of the different kinds of photodermatosis found in this particular study., Methods: This study was descriptive, retrospective, and mono-centric. It was based on 100 consecutive patients, who have been phototested in a French University Hospital from 2014 to 2018. Phototesting included determination of the minimal erythematous dose (MED), UVA and UVB phototests, and photopatch testing., Results: The use of phototesting led to 60% of photodermatosis diagnosis and formally eliminated the latter in 13% of the cases. The diagnosis remained undetermined in 27% of the cases. Nineteen cases of polymorphous light eruption (PLE), 14 cases of photocontact dermatitis (PCD), 10 cases of solar urticaria, 8 cases of photo-aggravated atopic eczema, 5 cases of chronic actinic dermatitis, and 2 cases of systemic photosensitization were diagnosed. The allergens involved in PCD were topical non-steroidal anti-inflammatory drug (NSAID) in 9 cases, sunscreens in 3 cases, and fragrance in 2 cases. The average amount of time between the first symptoms and actual phototesting was about 7,5 years., Conclusion: This study confirms phototesting is truly useful. PLE was the most common form of photodermatosis, followed by PCD and solar urticaria. As photodermatosis could imply severe diseases sometimes requiring hospitalization, it is critical to maintain this expertise., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

(1) Background: As outcome of patients with metastatic melanoma treated with anti-PD1 immunotherapy can vary in success, predictors are needed. We aimed to predict at the patients' levels, overall survival (OS) and progression-free survival (PFS) after one year of immunotherapy, based on their pre-treatment 18F-FDG PET; (2) Methods: Fifty-six metastatic melanoma patients-without prior systemic treatment-were retrospectively included. Forty-five 18F-FDG PET-based radiomic features were computed and the top five features associated with the patient's outcome were selected. The analyzed machine learning classifiers were random forest (RF), neural network, naive Bayes, logistic regression and support vector machine. The receiver operating characteristic curve was used to compare model performances, which were validated by cross-validation; (3) Results: The RF model obtained the best performance after validation to predict OS and PFS and presented AUC, sensitivities and specificities (IC95%) of 0.87 ± 0.1, 0.79 ± 0.11 and 0.95 ± 0.06 for OS and 0.9 ± 0.07, 0.88 ± 0.09 and 0.91 ± 0.08 for PFS, respectively. (4) Conclusion: A RF classifier, based on pretreatment 18F-FDG PET radiomic features may be useful for predicting the survival status for melanoma patients, after one year of a first line systemic treatment by immunotherapy.

Background: Late-onset adverse events (AEs) of anti-programmed cell death 1 (anti-PD1) antibodies have not been systematically described., Objectives: The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered for at least 2 years in a real-life setting., Methods: Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow up of unresectable stage III or IV melanoma. The study included 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). Fifty-three patients received nivolumab and 66 patients received pembrolizumab., Results: AEs occurred in 99 patients (83%) with a median time of 13.3 months (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first 2 years of treatment) and treatment duration (P = .02 and P = .03, respectively)., Conclusions: Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs., Competing Interests: Conflicts of interest Dr Nardin has a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, Novartis, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre. Dr. Dalle is an employee of Sanofi, has Stock and Other Ownership Interests in Sanofi, has a Consulting or Advisory Role with Bristol-Myers Squibb, received Research Funding from Bristol-Myers Squibb, and reports travel, accommodations, and expenses from Bristol-Myers Squibb and Pierre Fabre. Dr Leccia has No Relationships to Disclose. Dr Mortier received honoraria from Bristol-Myers Squibb and MSD Oncology, received Research Funding from MSD Oncology and Pierre Fabre, and received travel, accommodations, and expenses from Bristol-Myers Squibb, Novartis, Roche/Genentech, and Roche/Genentech. Dr Dalac-Rat received honoraria from Bristol-Myers Squibb, MSD, and Novartis, reports a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, and Novartis, is on the Speakers' Bureau for Bristol-Myers Squibb, reports Research Funding from Bristol-Myers Squibb, MSD, and Novartis, and reports travel, accommodations, and expenses from Bristol-Myers Squibb. Dr Dutriaux received honoraria from Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre reports a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre. Dr Legoupil received honoraria from Bristol-Myers Squibb and MSD, reports a Consulting or Advisory Role with Bristol-Myers Squibb and Pierre Fabre, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, MSD, and Pierre Fabre. Dr Montaudié reports a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre, received Research Funding from Leo Pharma and Novartis, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, Novartis, and Pierre Fabre. Dr Dereure reports a Consulting or Advisory Role with Bristol-Myers Squibb, Genevrier, Kiowa Kirin, Leo Pharma, MSD, Novartis, Pierre Fabre, and Recordati, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, Novartis, Pierre Fabre, and Recordati. Dr De Quatrebarbes is on the Speakers' Bureau for Bristol-Myers Squibb and Janssen-Cilag and reports travel, accommodations, and expenses from BMS and MSD Oncology. Dr Granel-Brocard has no relationships to disclose. Dr Le-Bouar has no relationships to disclose. Dr Charles has no relationships to disclose. Dr Brunet-Possenti reports a Consulting or Advisory Role with Bristol-Myers Squibb and Sanofi. Dr Dreno received honoraria from Bristol-Myers Squibb, Merck, Pierre Fabre, Roche, and Sanofi, reports a Consulting or Advisory Role with Bristol-Myers Squibb, Pierre Fabre, Roche, and Sanofi, and reports travel, accommodations, and expenses from Bristol-Myers Squibb, Pierre Fabre, and Roche. Dr Lefevre has no relationships to disclose. Dr Allayous reports travel, accommodations, and expenses from Amgen, Bristol-Myers Squibb, and Roche. Dr Lebbe reports honoraria from Amgen, Bristol-Myers Squibb, Incyte, MSD, Novartis, Pfizer, Pierre Fabre, and Roche, reports a Consulting or Advisory Role with Amgen, Bristol-Myers Squibb, Merck Serono, MSD, Novartis, Roche, and Sanofi, is on the Speakers' Bureau for Amgen, Bristol-Myers Squibb, MSD, Novartis, and Roche, received Research Funding from Bristol-Myers Squibb, and Roche, reports travel, accommodations, and expenses from Bristol-Myers Squibb and MSD, and reports other relationship with Avantis Medical Systems., (Copyright © 2021. Published by Elsevier Inc.)

Hymenoptera venom anaphylaxis is the most frequent cause of anaphylaxis and responsible for about 20% of all fatal anaphylaxis cases in adults. We report two cases of fatal hymenoptera venom anaphylaxis with undiagnosed underlying mastocytosis and review the risk factors for severe or fatal hymenoptera venom anaphylaxis, as well as the specificities of its association with mastocytosis. As hymenoptera venom allergic patients with underlying clonal mast cell disorder generally lack typical skin lesions of mastocytosis, its diagnosis can easily be missed, underscoring the importance and need for diagnostic strategies in order to correctly identify these patients. Predominant cardiovascular symptoms in the absence of urticaria or angioedema following an insect sting are suggestive of underlying clonal mast cell disorder, and should be distinguished from panic attack or vasovagal syncope. Similarly, an unexplained syncope or an "idiopathic" anaphylaxis might reveal mastocytosis or hereditary alpha-tryptasemia. Acute and basal serum tryptase measurements should always be integrated in the diagnostic work-up of an insect sting reaction or unexplained syncope or shock of any origin., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib., Materials and Methods: This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment., Results: Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months)., Conclusion: Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms., Competing Interests: Disclosure EMN: Consulting or advisory role: Novartis, Pierre Fabre, Bristol-Myers Squibb, MSD. EM: Consulting or advisory role: MSD, Pierre Fabre, Novartis, Sanofi; research funding: MSD (Inst); travel, accommodations, expenses: MSD Oncology, Pierre Fabre, Novartis. NM: Consulting or advisory role or research funding: Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Merck, Sanofi, Sun Pharmaceutical Industries. MB-B: Research funding: Roche; consulting or advisory role: Sun Pharmaceutical Industries. NB-S: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries. LM: Consulting or advisory role: Sanofi, Sun Pharmaceutical Industries, MSD Oncology, Bristol-Myers Squibb, Novartis. The remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our aim was to analyse whether biomarkers extracted from baseline 18 F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18 F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80-1), 56.1% (IC 95 37.1-85) and 19% (IC 95 0.06-60.2) and hazard ratios were respectively 0.11 (IC 95 0.025-0.46), P = 0.0028, 1.2 (IC 95 0.48-2.8), P = 0.74 and 5.9 (IC 95 2.5-14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials., (© 2021. The Author(s).)

Purpose: Melanoma's incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined BRAF and MEK targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population., Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 ≤ 65-year-old (yo), group 2 > 65 yo, analyzed for tolerance and efficacy., Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3-4: 28% in group 1 and 39% in group 2 ( p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5-27.9) and 16.3 M (CI: 14.5-26.9), respectively ( p = 0.8). Median progression free survival was 7.8 M (6.4-9.9) and 7.7 M (CI: 5.8-11.3) ( p = 0.4). Objective response rate was 59% and 50% ( p = 0.6)., Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable.

This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real-world clinical practice in France using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric-Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second- or subsequent-line therapy. The median durations of progression-free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0-34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3-5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real-world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population., (© 2021 UICC.)

Background: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy., Patients and Methods: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out., Results: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI., Conclusion: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution., Competing Interests: Disclosure StD reports institutional research funding from Roche; institutional research funding and nonfinancial support from Bristol-Myers Squibb (BMS); and an immediate family member who is employed by Sanofi and owns stock or other ownership interest in the company. LM reports personal fees and nonfinancial support from Roche, Novartis, BMS, and Merck Sharp & Dohme (MSD) outside the submitted work. OD reports personal fees and nonfinancial support from BMS, MSD, Pierre Fabre, Novartis, Leo Pharma, Genevrier, Kyowa Kirin, Recordati Rare Diseases outside the submitted work. SoD received research funding and travel costs covered by BMS and MSD. Travel costs covered by Pierre Fabre. CD reports personal fees from Roche, BMS, Novartis, MSD, and Pierre Fabre Laboratories outside the submitted work. PS reports research funding and personal fees from Roche; grants, personal fees, and nonfinancial support from BMS, MSD, Novartis, and Pierre Fabre Laboratories; and personal fees from Array, Sanofi, and Merck, all outside the submitted work. J-PA reports personal fees from BMS, grants from BMS, Novartis, and MSD, during the conduct of the study. EM reports grants, personal fees, and nonfinancial support from MSD; personal fees from Sanofi and Novartis; personal fees and nonfinancial support from BMS; and nonfinancial support from Pierre Fabre Laboratories, all outside the submitted work. JDQ reports nonfinancial support from BMS, MSD, and Janssen outside the submitted work. FA reports personal fees and nonfinancial support from Novartis, MSD, and Roche outside the submitted work. TL reports research funding and personal fees from Roche and personal fees from BMS, MSD, Novartis, Pierre Fabre Laboratories, and Incyte, all outside the submitted work. P-ES reports travel accomodations -meetings by BMS, Novartis, MSD, and Sanofi. J-JG reports personal fees and nonfinancial support from BMS, Roche, MSD, Novartis, Merck, Amgen, Pierre Fabre Laboratories, Sanofi, and Pfizer and nonfinancial support from Amgen, all outside the submitted work. CA reports travel accommodations-meetings by Roche, BMS, and Amgen. CL reports grants and personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, personal fees from Merck Serono, personal fees from Sanofi, outside the submitted work. HM reports institutional research funding from LeoPharma; institutional research funding, personal fees, and nonfinancial support from BMS; personal fees from Pierre Fabre Laboratories and MSD; and nonfinancial support from Novartis, all outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Dermatofibrosarcoma protuberans (DFSP) is a soft-tissue sarcoma characterized by a high risk of local infiltration. The identification of the COL1A1-PDGFB t(17;22) translocation activating the PDGF pathway led to the use of imatinib in unresectable DFSP, with a response rate of 36-80%. Pazopanib is a multitarget tyrosine kinase inhibitor approved for soft-tissue sarcomas. We conducted a phase II study of patients with unresectable DFSP to evaluate the efficacy and safety of pazopanib. Patients received 800 mg of pazopanib daily. The primary endpoint was the objective response rate defined as the reduction of the largest diameter of the tumor by ≥30% at 6 months or at surgery. A total of 23 patients, including one pretreated with imatinib, were enrolled. With a median follow-up of 6.2 months (interquartile range = 5.6-7.8 months), five patients (22%, 95% confidence interval = 7-22%) had a partial response to pazopanib. The best objective response rate was 30% (95% confidence interval = 13-53%) using Response Evaluation Criteria in Solid Tumors. One patient with metastatic DFSP previously treated with imatinib died after 2.4 months. Nine patients (39%) discontinued the treatment owing to adverse events. Pharmacodynamics analyses of tumor samples were conducted: the enrichment of EGF and the EGFR-associated gene panel was associated with resistance, suggesting that EGFR-targeted therapies could be a therapeutic option to explore in DFSP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01059656., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy., Methods: Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/anti-PD-L1 were collected., Results: Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, P=4.10 -4 ) and disease control rates (73% versus 52%, P=7.10 -3 ) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found (P=3.10 -1 ). The PFS upon the first ICPi (PFS1) was longer than after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, P=2.10 -3 ). A longer PFSR was obtained in patients with a longer PFS1 (P=6.10 -3 ), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, P=2.10 -3 ), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, P=1.10 -3 )., Discussion: Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Truncal acne is frequently overlooked in dermatological practice, even though it may result in scars and impact on self-esteem and body image. Therefore, it is important to identify the disease early in order to initiate treatment in time and, thus, to prevent it from worsening and resulting in physical and psychological sequelae. The aim of this review is to provide an overview of what is currently known about truncal acne, its prevalence, aetiology and physiopathology, how its severity is currently evaluated, how to differentiate it from other skin afflictions and current treatment options. A review of literature considering the issue of truncal acne published up to 2019 and available from PubMed was conducted, and in total, 76 articles were selected from PubMed. Currently, only little information about truncal acne is available. Considered as having the same pathophysiology as facial acne, the clinical picture and treatment response seem to differ. Specific acne severity grading systems and quality of life questionnaires as well as a specific treatment algorithm are still lacking. Filling this gap should allow clinicians to assess truncal acne in the best possible way, choosing suitable treatment options, helping patients to improve treatment adherence and quality of life and finally allowing a better management of truncal acne. In conclusion, more knowledge is required to treat more efficiently truncal acne., (© 2020 European Academy of Dermatology and Venereology.)

Purpose: To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs)., Patients and Methods: Patients, predominantly men, with their CSSCs' immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort's objective response rate at week 15 (ORR W15 ). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORR W15 difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival., Results: Median age of all patients was 79 years. The primary cohort's ORR W15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORR W15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; P = .02). Responders' W15 total FACT-G score had improved ( P = .025) compared with nonresponders., Conclusion: First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.

Background: Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma., Aim: To confirm previously observed preventive effects of TIL + IL2 in a subgroup of patients with relapsing metastatic stage III melanoma., Methodology: Open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection. Patients received TIL + IL2 or abstention. TIL + IL2 was administered within 8 weeks after lymph node resection and 4 weeks after. Disease-free survival was assessed every 2 months up to month 18, every 3 months up to month 36 and every 4 months up to 5 years. A once-a-year follow-up was scheduled beyond the five-year follow-up. Safety was assessed throughout the trial., Results: Overall, 49 patients accounted for the modified intent-to-treat and 47 for the PP. Slightly more male than female patients participated; mean age was 57.7 ± 11.4 years in the TIL + IL2 group and 53.5 ± 13.0 years in the abstention group. After 5 years of follow-up, 11/26 patients in the TIL + IL2 group and 13/23 in the abstention group had relapsed. There was no statistical difference between the groups (HR: 0.63 CI 95% [0.28-1.41], p = 0.258), nine patients in the TIL + IL2 and 11 in the abstention group died with no significant difference between the two groups (HR: 0.65 CI95% [0.27 - 1.59], p = 0.34). Safety was good., Conclusion: We did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α.

Background: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma., Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies., Materials and Methods: A subgroup data analysis., Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients., Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.

Background: Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs)., Objective: To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs., Methods: A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed., Results: Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs., Limitations: Due to the retrospective observational design of the study., Conclusions: Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

There is increasing evidence that T-cell receptor (TCR) repertoire diversity can be a predictive biomarker of immune responses in cancer patients. However, the characteristics of the T-cell repertoire together with its prognostic significance in melanoma patients and impact on disease progression remain unknown. We investigated the combinatorial TCR repertoire diversity by semi-quantitative multi-N-plex PCR in peripheral blood samples from 44 melanoma patients together with seven matched metastatic lymph nodes and explored its potential predictive value on clinical prognosis. The diversity was quantified by calculating both richness (number of different specificities) and evenness (relative abundance of the different specificities). Our results revealed that a higher TCR repertoire diversity in blood of patients was associated with a longer PFS, while divpenia (low repertoire diversity) was linked with poor prognosis. The diversity was significantly higher in patients undergoing late relapse and long survival compared to patients who progressed rapidly. Interestingly, the TCR repertoire diversity in tumor may have a potential prognostic value. Thus, our study highlights that the TCR repertoire diversity is a prognostic indicator of clinical outcome in patients with melanoma., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Acne vulgaris has increased in women over the past 10 years; it currently affects 20-30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone's efficacy in order to establish it as an alternative to cyclines., Methods: Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months., Discussion: The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage., Trial Registration: ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.

Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess the safety of combined ICI and TT as a rescue line in real-life clinical practice. We conducted a study within the prospective French multicentric MelBase cohort, including patients treated with a combination of anti-PD1 (pembrolizumab/nivolumab) and BRAF inhibitor (BRAFi: dabrafenib/vemurafenib) and/or MEK inhibitors (MEKi: trametinib/cobimetinib) for BRAF mutated or wild-type advanced melanoma. Fifty-nine patients were included: 30% received the triple combination, 34% an anti-PD1 and BRAFi, and 36% an anti-PD1 and MEKi. Grade 3-4 adverse events occurred in 12% of patients. Permanent discontinuation or dose reduction of one of the treatments for toxicity was reported in 14% and 7% of patients, respectively. In the BRAF wild-type subgroup, treatment with MEKi and anti-PD1 induced a tumor control rate of 83% and median progression-free survival of 7.1 months. The combination of anti-PD1 and BRAFi and/or MEKi was a safe rescue line for advanced melanoma patients previously treated with ICI/TT. The benefit of these combinations, specifically anti-PD1 and MEKi in BRAF wild-type melanoma patients, needs to be prospectively studied.

Acne may significantly impact quality of life, self-esteem and self-worth. The aim of this paper was to provide an overview of the knowledge and perception of acne and its risk factors in adolescents and young adults. The most critical issues reported for an optimal management of this specific population were identified. A PubMed literature review of results from patient-oriented surveys published between 2007 and 2018 was conducted. Two different types of survey were used: those using either validated questionnaires or specifically developed questionnaires. No consistency or directly comparable data with regards to age, onset, duration, severity and treatment of acne and by whom and where data were collected were observed. Acne affected female patients psychologically more than male patients. The majority referred to their treating physician in order to obtain information, and all surveys pointed out that specific treatment programs would allow to increase awareness about acne. Beliefs, traditions and economic factors continue to impact the perception of and treatment choices for acne in almost all countries and cultures, maintaining the improvement of awareness about acne a major global health challenge. In conclusion, identifying, considering and managing the patient's concerns about acne may improve the young patient's well-being and thus decrease additional healthcare expenses for emerging psychological comorbidities. This can be achieved by creating substantial and structured awareness through local and global information campaigns via the treating physicians, Internet, social networks and education., (© 2019 European Academy of Dermatology and Venereology.)