Drugs
-
Oral pomalidomide (Imnovid® [EU]; Pomalyst® [USA]) in combination with dexamethasone (in the EU), is approved in several countries for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy (or progression within the last 60 days in the USA). The key therapeutic mechanisms of action of pomalidomide, a thalidomide analogue, reside in its immunomodulatory, antiproliferative and anti-angiogenic effects. ⋯ In general, improvements in these clinical outcomes with pomalidomide plus low-dose dexamethasone treatment were also observed in subgroups of patients, including those refractory to lenalidomide, bortezomib or both drugs, those who had received several prior antimyeloma therapies, patients with renal impairment, elderly patients and those with a high-risk cytogenetic profile. Thus, combination therapy with pomalidomide plus low-dose dexamethasone is an important emerging treatment option for use as salvage therapy in patients with relapsed and refractory multiple myeloma.
-
Treatment of multiple sclerosis (MS) is challenging: disease-modifying treatments (DMTs) must both limit unwanted immune responses associated with disease initiation and propagation (as T and B lymphocytes are critical cellular mediators in the pathophysiology of relapsing MS), and also have minimal adverse impact on normal protective immune responses. In this review, we summarize key preclinical and clinical data relating to the proposed mechanism of action of the recently approved DMT teriflunomide in MS. ⋯ In agreement with the results obtained in these model systems, phase 3 clinical trials of teriflunomide in patients with MS have consistently shown that teriflunomide provides a therapeutic benefit, and importantly, does not cause clinical immune suppression. Taken together, these data demonstrate how teriflunomide acts as a selective immune therapy for patients with MS.
-
Review Comparative Study
Trastuzumab emtansine: a review of its use in patients with HER2-positive advanced breast cancer previously treated with trastuzumab-based therapy.
Trastuzumab emtansine (Kadcyla™) is an antibody-drug conjugate consisting of the humanized anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab covalently linked to the highly potent microtubule inhibitory drug DM1 (a cytotoxic derivative of maytansine) via a stable thioether linker. Intravenous trastuzumab emtansine was recently approved for use in patients with HER2-positive, unresectable, locally advanced (in the EU) or metastatic (in the USA and EU) breast cancer who had previously received trastuzumab and a taxane (separately or in combination), making it the first antibody-drug conjugate approved in this indication. ⋯ Trastuzumab emtansine was generally well tolerated in this study, with <6% of patients discontinuing treatment because of adverse events. Based on its efficacy and favourable tolerability, the US National Comprehensive Cancer Network guidelines recommend trastuzumab emtansine as the preferred option in patients with HER2-positive metastatic breast cancer who have received previous trastuzumab-based therapy.
-
It is unanimously accepted that there is an unmet need for pain medications that are both effective and safe. Unfortunately, no really novel analgesics have been approved over the past three decades. In view of both experimental and clinical evidence of a major role for nerve growth factor (NGF) in the generation and maintenance of a wide range of pain states, drug discovery efforts focusing on the development of anti-NGF agents have aroused particular interest. ⋯ After an Arthritis Advisory Committee meeting held in March 2012, pharmaceutical companies negotiated with the FDA on the conditions for restarting clinical studies. Although the FDA lifted its clinical hold, there remain many unresolved issues about the long-term efficacy and safety of anti-NGF mAbs. While acknowledging that the future of these drugs is unforeseeable, it appears that they may not be the safe and effective painkillers that have been awaited for decades.
-
A combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®)) in one tablet with a fixed 2:1 ratio is available for the treatment of patients with severe pain, which can only be adequately managed with opioid analgesics. The aim of this formulation is to counteract opioid-induced constipation through the local antagonist effect of naloxone in the gut wall, while maintaining analgesia due to the low bioavailability of oral naloxone. Three large, 12-week, randomized, double-blind, phase III trials in patients with moderate to severe, chronic, non-malignant pain, plus a prospectively planned pooled analysis of two of these studies, demonstrated that oxycodone/naloxone PR improved bowel function, as measured by the bowel function index, compared with oxycodone PR. ⋯ Of note, numerically lower rates of constipation were observed in the oxycodone/naloxone PR group compared with the oxycodone PR group. A cost-utility analysis predicted that oxycodone/naloxone PR would be a cost-effective option compared with oxycodone PR in patients with non-malignant pain. Although more comparative data are needed, oxycodone/naloxone PR is an effective option for use in patients with severe chronic pain, particularly among those with opioid-induced constipation.