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Summary: Background: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. Objectives: This is the final 42‐month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. Methods: Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent. The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety end points included adverse event monitoring and reporting. Results: The study enrolled 230 patients, 79 and 151 in the 200‐mg and 800‐mg groups, respectively, of whom 8% and 3.3% remained on treatment by the 42‐month cutoff, respectively. The ORRs by central review were 56% [95% confidence interval (CI) 43–68] for laBCC and 8% (95% CI 0·2–36) for mBCC in the 200‐mg group and 46·1% (95% CI 37·2–55·1) for laBCC and 17% (95% CI 5–39) for mBCC in the 800‐mg group. No new safety concerns emerged. Conclusions: Sonidegib demonstrated sustained efficacy and a manageable safety profile. The final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC. What's already known about this topic? Basal cell carcinoma (BCC) is usually treatable with surgery or radiation therapy, but there are limited treatment options for patients with advanced BCC.Sonidegib, a hedgehog pathway inhibitor approved for the treatment of advanced BCC, demonstrated clinically relevant efficacy and manageable safety in prior analyses of the phase II randomized, double‐blind BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. What does this study add? This final 42‐month analysis of BOLT is the longest follow‐up available for a hedgehog pathway inhibitor.Clinically relevant efficacy results were sustained from prior analyses, with objective response rates by central review of the approved 200‐mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC.No new safety concerns were raised.The results confirmed sonidegib as a viable long‐term treatment option for patients with advanced BCC. Linked Comment:Fife. Br J Dermatol 2020; 182:1322–1323. [ABSTRACT FROM AUTHOR]

Background: α(v) integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-α(v)-integrin monoclonal antibody.Methods: In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics.Results: No statistically significant differences in efficacy were observed between groups. In the dacarbazine+placebo, dacarbazine+intetumumab, 10 mg kg(-1) intetumumab, and 5 mg kg(-1) intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of complete+partial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred.Conclusion: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma. [ABSTRACT FROM AUTHOR]

Background and study aim: The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE). Patients and methods: A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and smallbowel findings. Results: Intestinal blood losswas suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention- to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0% in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma. Conclusions: SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), with an increasing incidence worldwide. Currently, excision of the tumour with histological control is the standard therapy. However, high incidence rates have led to concern about the economic burden imposed by BCC management in many countries. Imiquimod is a member of a novel class of immune response modifiers (IRM), which works by using the toll-like receptor (TLR)-7. Although the exact mode of action is so far unknown, it is suggested to induce the expression of different cytokines like interleukin (IL)-1, IL-6, IL-12, interferon (IFN)-α and tumour necrosis factor (TNF)-α, which stimulate or enhance both the innate immune system and the cell-mediated immune response. Pre-clinical studies have indicated the potential of this TLR-7 agonist for the treatment of precancers and tumours in humans. A number of Phase II trials have demonstrated the efficacy of imiquimod for the treatment of BCC, although the most appropriate dosing regimen is being confirmed in Phase III studies. Imiquimod 5% cream for the treatment of mainly superficial BCC appears to be an effective and well-tolerated treatment option. [ABSTRACT FROM AUTHOR]

The skin reaction to radiation is regularly monitored in order to detect enhanced radiosensitivity of the patient, unexpected interactions (e.g. with drugs) or any inadvertent overdosage. It is important to distinguish secondary disease from radiation reaction to provide adequate treatment and to avoid unnecessary discontinuation of radiotherapy. A case of bullous eruption or blisters during radiotherapy of the breast is presented. Differential diagnoses bullous pemphigoid, pemphigus vulgaris, and bullous impetigo are discussed and treatment described. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented to report on a case of bullous drug dermatosis in a patient with metastatic malignant melanoma under an immunotherapeutic regimen of interleukin-2.

The identification of cancer stem cells in various malignancies led to the hypothesis that these cells have the exclusive ability of self-renewal, contribute to the plasticity of the tumours and may be the cause for ineffective cancer therapies. Several markers of melanoma stem cells have been described in recent studies including CD133, CD166, Nestin and BMI-1. Further studies are necessary to identify, better define and understand the origin and function of cancer stem cells. If confirmed that cancer stem cells play an important role in malignancy, therapeutic strategies may need to be redirected towards these cells to circumvent the failure of conventional therapies. [ABSTRACT FROM AUTHOR]