BackgroundMetastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies.MethodsA systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]).ResultsThe indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 − 1.30), PFS (HR 1.05, 95% CI 0.79 − 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 − 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 − 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 − 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 − 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib.ConclusionsThis indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.

BackgroundRosacea is a common chronic skin condition that manifests as recurrent inflammatory lesions. Long-term treatment is required to control symptoms and disease progression, with topical treatments being the first-line choice. Ivermectin 1 % cream is a new once-daily (QD) topical treatment for the inflammatory lesions of rosacea, and it is important to compare the efficacy, safety, and tolerability of ivermectin with other currently available topical treatments.MethodsA systematic literature review was performed from January 2011 to June 2015, with articles published prior to 2011 retrieved from a Cochrane review on rosacea. Randomized controlled trials of the topical treatment of adult patients with moderate-to-severe papulopustular rosacea were identified from electronic databases and trial registers, and supplemented with data from clinical study reports. Mixed treatment comparisons (MTCs) were conducted to compare different treatments according to Bayesian methodology.Results57 studies were identified, with 19 providing data suitable for MTC. Ivermectin 1 % cream QD led to a significantly greater likelihood of success compared with azelaic acid 15 % gel twice-daily (BID) [relative risk (95 % credible interval): 1.25 (1.14–1.37)], and metronidazole 0.75 % cream BID [1.17 (1.08–1.29)] at 12 weeks. Ivermectin 1 % cream QD also demonstrated a significant reduction in inflammatory lesion count compared with azelaic acid 15 % gel BID [−8.04 (−12.69 to −3.43)] and metronidazole 0.75 % cream BID [−9.92 (−13.58 to −6.35)] at 12 weeks. Ivermectin 1 % cream QD led to a significantly lower risk of developing any AE or TRAE compared with azelaic acid 15 % gel BID [0.83 (0.71–0.97) and 0.47 (0.32–0.67), respectively].ConclusionsIvermectin 1 % cream QD appears to be a more effective topical treatment than other current options for the inflammatory lesions of rosacea, with at least an equivalent safety and tolerability profile, and could provide physicians and dermatologists with an alternative first-line treatment option.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2819-8) contains supplementary material, which is available to authorized users.

Background: Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies. Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib. Conclusions: This indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.

studies, respectively, was conducted. Methods: A Bayesian ITC was performed on efficacy and safety on the non-gBRCA data from NOVA (niraparib) and gBRCA wild type data from S19 (olaparib). Efficacy analyses compared investigator (INV) and independent review committee (IRC) assessed PFS hazard ratios (HR) and TFST HR. Safety analyses included odds ratios (OR) of any grade ≥ 3 adverse event (AE), AEs leading to dose interruption, reduction, and discontinuation. Results: HRs comparing olaparib and niraparib were 0.94 (95% credible interval 0.54-1.65) for investigator-assessed PFS, and 1.25 (0.67-2.30) for IRC PFS. TFST HR was 0.78 (0.47-1.30). No significant difference in efficacy between PARPi was observed. The corresponding ORs for AE were 0.34 (0.13-0.90), 0.54 (0.16-2.06), 0.16 (0.01-2.18) and 0.21 (0.04-1.21) for any grade ≥ 3 AE, and AE leading to dose interruption, discontinuation, and reduction, respectively. There was a significant reduction in the odds of any grade ≥ 3 AE. No significant difference in AE leading to dose interruption, reduction, and discontinuation. ConClusions: ITC shows no significant difference in efficacy between olaparib capsules and niraparib tablets as maintenance therapy in patients with non-gBRCAm PSROC following response to chemotherapy. Olaparib shows significantly reduced odds compared with niraparib for any grade ≥ 3 AE. No significant difference was observed in AEs leading to modification in drug administration.

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