Drugs

Barnfield, Paul; Ellis, Peter

doi: 10.1007/s40265-016-0628-6pmid: 27557830

Platinum-based doublet chemotherapy with or without bevacizumab is the standard of care for the initial management of advanced and metastatic non-small cell lung cancer (NSCLC) without a targetable molecular abnormality. However, the majority of patients with NSCLC will ultimately develop resistance to initial platinum-based chemotherapy, and many remain candidates for subsequent lines of therapy. Randomised trials over the past 10–15 years have established pemetrexed (non-squamous histology), docetaxel, erlotinib and gefitinib as approved second-line agents in NSCLC without targetable driver mutations or rearrangements. Trials comparing these agents with other chemotherapy, evaluating the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to chemotherapy or the addition of another targeted agent to erlotinib or gefitinib have all failed to demonstrate an improvement in overall survival for patients with NSCLC. In contrast, recent data comparing therapy with novel monoclonal antibodies against programmed cell death 1 (PD-1) or PD ligand (PD-L1) pathway versus standard chemotherapy following platinum failure have demonstrated significant improvements in overall survival. Therapy with nivolumab or pembrolizumab would now be considered standard second-line therapy in patients without contraindication to immune checkpoint inhibitors. Atezolizumab also appears promising in this setting.

Kemp-Harper, Barbara; Horowitz, John; Ritchie, Rebecca

doi: 10.1007/s40265-016-0631-ypmid: 27566478

Heart failure (HF) is a major cause of hospital admission in the Western world, yet there remains a paucity of effective pharmacological management options. With the recent development of synthetic, next-generation nitroxyl (HNO) donors and their progress into clinical trials, it is timely to now provide an update on the therapeutic potential of HNO donors in the management of acute decompensated heart failure. In this article, we summarize current understanding of the pharmacology of HNO (in comparison with its redox sibling, nitric oxide), its spectrum of cardioprotective actions, and efforts to translate these into the clinic. Future research directions for this exciting new class of HF drugs are also considered.

Kelly, Yanna; Blanco, Aline; Tosti, Antonella

doi: 10.1007/s40265-016-0629-5pmid: 27554257

Androgenetic alopecia (AGA) is characterized by a non-scarring progressive miniaturization of the hair follicle in predisposed men and women with a pattern distribution. Although AGA is a very prevalent condition, approved therapeutic options are limited. This article discusses the current treatment alternatives including their efficacy, safety profile, and quality of evidence. Finasteride and minoxidil for male androgenetic alopecia and minoxidil for female androgenetic alopecia still are the therapeutic options with the highest level evidence. The role of antiandrogens for female patients, the importance of adjuvant therapies, as well as new drugs and procedures are also addressed.

Garnock-Jones, Karly

doi: 10.1007/s40265-016-0627-7pmid: 27510503

Intravenous fosaprepitant dimeglumine (Emend® for injection, IVEmend®; henceforth referred to as fosaprepitant) is a prodrug of and is rapidly converted to the antiemetic aprepitant, and is approved in several countries worldwide (as part of an antiemetic regimen) for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy (HEC and MEC). This narrative review discusses the pharmacological properties of intravenous fosaprepitant and its clinical efficacy and tolerability in the prevention of nausea and vomiting associated with HEC and MEC. In large, randomized phase III clinical trials, a single intravenous dose of fosaprepitant 150 mg was an effective and generally well tolerated addition to an antiemetic regimen that included dexamethasone and a serotonin 5-HT3 receptor antagonist in adult cancer patients undergoing treatment with HEC or MEC. It was also noninferior to an oral aprepitant-based regimen in adult cancer patients undergoing HEC treatment. The tolerability profile of a fosaprepitant-based regimen was typical of that in patients receiving emetogenic chemotherapy, and adverse events were generally consistent with those observed with an aprepitant-based regimen. Fosaprepitant provides a useful addition to antiemetic therapy regimens.

Lamb, Yvette; Scott, Lesley

doi: 10.1007/s40265-016-0630-zpmid: 27530616

Intramuscular incobotulinumtoxinA (Xeomin®) is indicated for the treatment or improvement of adult patients with upper limb spasticity (featured indication), cervical dystonia, blepharospasm and glabellar lines. It is a highly purified formulation of botulinum toxin type A that inhibits acetylcholine signalling at neuromuscular junctions, reducing muscle hypertonia. This narrative review discusses the clinical use of incobotulinumtoxinA in adults with upper limb spasticity and summarizes its pharmacological properties. In single-treatment phase 3 trials, compared with placebo, incobotulinumtoxinA treatment improved muscle tone, global spasticity, functional spasticity-related disability and some aspects of carer burden in adults with upper limb spasticity. These beneficial effects of incobotulinumtoxinA on muscle tone were generally maintained in extension studies, in which up to five additional incobotulinumtoxinA treatments were administered. Functional spasticity-related disability and carer burden were also reduced during longer-term incobotulinumtoxinA treatment. IncobotulinumtoxinA was generally well tolerated in clinical trials, with relatively few patients experiencing treatment-related adverse events, most of which were of mild to moderate intensity. No neutralizing antibodies that would potentially cause secondary nonresponse against incobotulinumtoxinA were detected after single and multiple treatments in these trials or in phase 3 and 4 trials of incobotulinumtoxinA in other indications, which may be an advantage of this purified formulation. Further research would help to more fully determine the impact of neurotoxin purification in terms of reducing the potential risk of immunogenic responses during long-term treatment. Hence, incobotulinumtoxinA is a useful treatment option for upper limb spasticity in adult patients.

Keating, Gillian

doi: 10.1007/s40265-016-0632-xpmid: 27550544

The hepatitis C virus (HCV) NS5A replication complex inhibitor daclatasvir (Daklinza®) is indicated for use in combination with sofosbuvir, with or without ribavirin, in a pangenotypic all-oral regimen. In patients with chronic HCV genotype 1 or 3 infection without cirrhosis, a 12-week regimen of daclatasvir plus sofosbuvir achieved high sustained virological response rates 12 weeks’ post-treatment (SVR12), regardless of prior treatment experience, according to the results of the AI444040 and ALLY-3 trials. In the ALLY-3+ trial, high SVR12 rates were achieved with a 12- or 16-week regimen of daclatasvir plus sofosbuvir and ribavirin in patients with chronic HCV genotype 3 infection and advanced fibrosis or compensated cirrhosis. A daclatasvir plus sofosbuvir-based regimen demonstrated efficacy in patients with chronic HCV genotype 1, 3 or 4 infection and advanced cirrhosis or post-transplant recurrence in the ALLY-1 trial, and in patients co-infected with HCV genotype 1, 3 or 4 and HIV-1 in the ALLY-2 trial. Results of clinical trials were supported by real-world data from early-access programmes that included high numbers of patients who would have been excluded from phase 3 trials because of advanced disease and/or concomitant medical conditions. Daclatasvir plus sofosbuvir with or without ribavirin was generally well tolerated. In conclusion, an all-oral regimen comprising daclatasvir plus sofosbuvir with or without ribavirin is an important option for use in treatment-naive or treatment-experienced patients with chronic HCV genotype 1, 3 or 4 infection, including in patients with advanced liver disease, post-transplant recurrence and HIV-1 co-infection.

Burness, Celeste; Duggan, Sean

doi: 10.1007/s40265-016-0633-9pmid: 27568360

Trifluridine/tipiracil (Lonsurf®) is a novel, orally active, antimetabolite agent comprised of trifluridine, a thymidine-based nucleoside analogue, and tipiracil, a potent thymidine phosphorylase inhibitor. Trifluridine is incorporated into DNA via phosphorylation, ultimately inhibiting cell proliferation. Tipiracil increases systemic exposure of trifluridine when coadministered. Trifluridine/tipiracil has recently been approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for, current standard chemotherapy and biological therapy in the EU and USA and in unresectable advanced or recurrent CRC in Japan. The approved regimen of oral twice-daily trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) significantly improved overall survival and progression-free survival and was associated with a significantly higher disease control rate than placebo when added to best supportive care in the multinational, pivotal phase III trial (RECOURSE) and a phase II Japanese trial. Trifluridine/tipiracil was associated with an acceptable tolerability profile, with adverse events generally being managed with dose reductions, temporary interruptions in treatment or administration of granulocyte-colony stimulating factor. The most common grade 3–4 adverse events (≥10 %) were anaemia, neutropenia, thrombocytopenia and leukopenia. In conclusion, trifluridine/tipiracil is a useful additional treatment option for the management of mCRC in patients who are refractory to, or are not considered candidates for, currently available therapies.

Greig, Sarah

doi: 10.1007/s40265-016-0634-8pmid: 27577550

Brodalumab (Lumicef®) is a human monoclonal immunoglobulin G antibody that is being developed by Kyowa Hakko Kirin in Japan, where it has been approved for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. Brodalumab binds with high affinity to interleukin (IL)-17 receptor A, thereby inhibiting several pro-inflammatory cytokines from the IL-17 family. Regulatory applications for brodalumab in plaque psoriasis are also under review in the USA, EU and Canada. This article summarizes the milestones in the development of brodalumab leading to this first approval for the treatment of psoriasis.