The RR of developing all-grade pruritus during treatment with pembrolizumab as compared to the chemotherapy controls was 49.9 (95% CI: 3.0C806.0; P=0.006). The incidence of high-grade pruritus was low with both drugs [nivolumab C 0.5% (95% CI: 0.2C1.3%) in 2/1126 patients analyzed using the fixed-effects model; pembrolizumab C 2.3% (95% CI: 0.7C7.6%) in 1/177 patients analyzed using the fixed-effects model]. [pembrolizumab: incidence, 20.2% (RR=49.9); nivolumab: incidence, 13.2% (RR=34.5)] and vitiligo [pembrolizumab: incidence, 8.3% (RR=17.5); nivolumab: 7.5% (RR=14.6)]. Interestingly, all the vitiligo events were reported in trials investigating melanoma. The RR Drofenine Hydrochloride for developing dermatologic toxicities in general, was 2.95 with pembrolizumab, and 2.3 with nivolumab. Conclusion We found that pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with ipilimumab. Knowledge of these findings is critical for optimal care, maintaining dose intensity, and health-related quality of life, in cancer patients receiving PD-1 inhibitors. mutational status, prior treatment with ipilimumab/platinum-based chemotherapy/antiangiogenic therapy, or PD-L1 expression).10,11 In general, these drugs inhibit the key immune-compromising interaction between the tumor cell PD-L1 (B7-H1)/PD-L2 (B7-DC) and T cell PD-1 receptors.12 In terms of AEs, their overall safety profiles appear impressive. However, the potential for developing dermatologic AEs remains significantmoreover, the pattern is understood to be different in frequency and character from most other chemotherapy and targeted therapy-induced AEs.13 Some of these AEs manifest with Rabbit polyclonal to IL22 signs of autoimmunity (immune-related adverse events, irAEs), and are thought to be due to treatment-related nonspecific hyperfunctioning of the immune system. Our current understanding mostly stems from the ipilimumab experience, wherein the development of rash, pruritus, alopecia, and vitiligo (in 20C30% of patients)14 may lead Drofenine Hydrochloride to anticancer therapy dose modifications and/or termination, besides impairing patients health-related quality of life (HRQoL). Since very little is known about PD-1 inhibitor-induced dermatologic AEs, we sought to determine the incidence and risk, and describe the clinical characteristics in patients evaluated at our oncodermatology program. PATIENTS AND METHODS Data sources and search strategy We conducted a systematic search of the literature to identify clinical trials of pembrolizumab and nivolumab, that reported dermatologic AEs. The Medline (via PubMed) and Thomson-Reuters Web of Science databases were searched for studies published between January, 1960, and July, 2015. The following generic drug names and synonyms were used as search terms: pembrolizumab (MK-3475/lambrolizumab/Keytruda) and nivolumab (BMS-963558/ONO-4538/MDX-1106/Opdivo). In addition, pertinent abstracts from the American Society of Clinical Oncologys (ASCO) and the European Society for Medical Oncologys (ESMO) annual meetings/congresses were reviewed. The latest manufacturers package inserts were also retrieved. Study selection and screening process Our selection criteria included all prospective clinical trials (and/or cohorts) that: 1) investigated the utility of pembrolizumab or nivolumab at the FDA-approved dose in the treatment of cancer; 2) clearly reported a dermatologic AE in their safety data, with or without the clinical severity grading; and 3) were published in the English language (Fig. 1). We excluded any trials that: 1) involved combination regimens with other therapies/modalities (e.g. targeted therapy, chemotherapy, radiation therapy, other immunotherapies); and 2) did not list a dermatologic AE exclusively in any arm/cohort (Fig 1). Within the trials included for analysis, for skin eruptions, data was recorded only for instances of rash; others e.g. rash maculopapular, macular/erythematous rash, pruritic rash, eczema, dermatitis, drug eruption were excluded because of possible duplication in reporting within the same trial (the excluded data was not significant). In the event of duplicates, ambiguity or publications reporting on the same study population, only the most recent, relevant and/or comprehensive publication (abstract/manuscript) was retained. Any discrepancy Drofenine Hydrochloride in selection was resolved by consensus. Open in a separate window Fig 1 Flow diagram showing the selection process for clinical trials included in the final analysis. Data extraction and Clinical Endpoints The data abstraction was conducted by two authors (V.R.B. and B.B.) independently and then reviewed. The variables extracted included the name of the first author, year of publication, clinical trial identifier (e.g. NCT#), study design, overall enrollment numbers, number of.