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Clinical Cancer Research : An Official... Sep 2023The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial... (Clinical Trial)
Clinical Trial
The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29-51] and a median response duration of 11.1 months (95% CI: 6.9-not evaluable). Guardant360 CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions, which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.
Topics: Adult; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutagenesis, Insertional; ErbB Receptors; Exons; Mutation; Protein Kinase Inhibitors
PubMed: 37022784
DOI: 10.1158/1078-0432.CCR-22-3713 -
JACC. CardioOncology Aug 2023•Mutations in the gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous mutations,... (Review)
Review
•Mutations in the gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation. Common side effects include acneiform rash, diarrhea, and paronychia. Osimertinib has also been associated with cardiomyopathy (∼1.4%-2.4%) and prolongation of the QT interval (2.7%).•In our experience, osimertinib-induced cardiomyopathy can be managed with the cessation of osimertinib and the initiation of guideline-directed therapy. Given that osimertinib is often the best available therapy, rechallenging with osimertinib often favors benefit over risk. Safe rechallenge with osimertinib is demonstrated in this case.
PubMed: 37614580
DOI: 10.1016/j.jaccao.2023.04.005 -
Dermatologic Therapy Jul 2021An increasing use of beta-blockers in dermatology has been described over the last 10 years, despite the fact that their use in diseases other than infantile... (Review)
Review
An increasing use of beta-blockers in dermatology has been described over the last 10 years, despite the fact that their use in diseases other than infantile hemangiomas is off-label. This review discusses the emerging role of topical beta-blockers in the treatment of infantile hemangioma, but also pyogenic granuloma, Kaposi sarcoma, wounds and nail paronychia. Data in literature demonstrate that topical beta-blockers are a safe and valid therapeutic option in numerous cutaneous diseases. Side effects are mainly restricted to the application site. Further studies and randomized trials may contribute to reinforce the role of topical beta-blockers in the dermatological armamentarium.
Topics: Adrenergic beta-Antagonists; Granuloma, Pyogenic; Humans; Sarcoma, Kaposi; Skin Diseases; Timolol
PubMed: 34075667
DOI: 10.1111/dth.15016 -
Journal of Clinical Oncology : Official... Sep 2023Although several agents targeting epidermal growth factor receptor () exon 20 insertions (ex20ins) have recently been approved by the US Food and Drug Administration,...
PURPOSE
Although several agents targeting epidermal growth factor receptor () exon 20 insertions (ex20ins) have recently been approved by the US Food and Drug Administration, toxicities related to the inhibition of wild-type (WT) are common with these agents and affect overall tolerability. Zipalertinib (CLN-081, TAS6417) is an oral EGFR tyrosine kinase inhibitor (TKI) with a novel pyrrolopyrimidine scaffold leading to enhanced selectivity for ex20ins-mutant versus WT with potent inhibition of cell growth in ex20ins-positive cell lines.
METHODS
This phase 1/2a study of zipalertinib enrolled patients with recurrent or metastatic ex20ins-mutant non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
RESULTS
Seventy-three patients were treated with zipalertinib at dose levels including 30, 45, 65, 100, and 150 mg orally twice a day. Patients were predominantly female (56%), had a median age of 64 years, and were heavily pretreated (median previous systemic therapies 2, range 1-9). Thirty six percent of patients had received previous non-ex20ins EGFR TKIs and 3/73 (4.1%) patients received previous EGFR ex20ins TKIs. The most frequently reported treatment-related adverse events of any grade included rash (80%), paronychia (32%), diarrhea (30%), and fatigue (21%). No cases of grade 3 or higher drug-related rash or diarrhea were observed at 100 mg twice a day or below. Objective responses occurred across all zipalertinib dose levels tested, with confirmed partial response (PR) observed in 28/73 (38.4%) response-evaluable patients. Confirmed PRs were seen in 16/39 (41%) response-evaluable patients at the dose of 100 mg twice a day.
CONCLUSION
Zipalertinib has encouraging preliminary antitumor activity in heavily pretreated patients with ex20ins-mutant NSCLC, with an acceptable safety profile, including low frequency of high-grade diarrhea and rash.
Topics: Humans; Female; Middle Aged; Male; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; ErbB Receptors; Exons; Mutation; Diarrhea; Protein Kinase Inhibitors
PubMed: 37384848
DOI: 10.1200/JCO.23.00152 -
Hand Clinics Aug 2020Clinically significant fungal infections of the upper extremity are uncommon but increasing They are classified based on anatomic location and epidemiology. The anatomic... (Review)
Review
Clinically significant fungal infections of the upper extremity are uncommon but increasing They are classified based on anatomic location and epidemiology. The anatomic categories that affect the hand include cutaneous, subcutaneous, and deep. Cutaneous infections are caused by organisms that metabolize keratin and can cause serious morbidity but are rarely fatal. Subcutaneous infections are similar to the cutaneous infections and are produced by low virulence organisms. Cutaneous and subcutaneous infections are most common and can be treated by primary care physicians and dermatologists. Deep infections are less common but can be fatal. Epidemiologic classifications include endemic and opportunistic infections.
Topics: Hand; Humans; Mycoses; Paronychia; Soft Tissue Infections
PubMed: 32586462
DOI: 10.1016/j.hcl.2020.03.009 -
Hand Clinics Aug 2020Infections are an important source of morbidity in pediatric hands that come from frequent exposure to mouths and other dangers while exploring the world. Although... (Review)
Review
Infections are an important source of morbidity in pediatric hands that come from frequent exposure to mouths and other dangers while exploring the world. Although Staphylococcus aureus is still the most common organism in pediatric hand infections, it is less common than in adults because pediatric patients are more likely to develop mixed aerobic/anaerobic infections or group A Streptococcus pyogenes infection. Pediatric patients with open physes potentially may sustain Seymour fractures of the distal phalanges that may become infected and sources for osteomyelitis if not recognized early.
Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Bites and Stings; Bites, Human; Child; Debridement; Hand; Humans; Osteomyelitis; Paronychia; Soft Tissue Infections; Tenosynovitis
PubMed: 32586465
DOI: 10.1016/j.hcl.2020.03.012 -
Indian Journal of Dermatology,... May 2023Nail cosmetics industry is growing at an enormous rate globally due to a surge in nail care all around the world. Various nail cosmetics are available, such as nail... (Review)
Review
Nail cosmetics industry is growing at an enormous rate globally due to a surge in nail care all around the world. Various nail cosmetics are available, such as nail polish along with its variants like shellacs, finishes, artificial nails, adornments, and nail polish removers. Nail cosmetics serve aesthetic as well as therapeutic purposes, with the end result being smooth, attractive nails. Nail grooming procedures have evolved from a basic manicure to many other advanced procedures like gel nails, nail tattooing, etc. Although a majority of nail cosmetics are considered safe, they may have potential complications, including allergic and irritant reactions, infections, and mechanical effects. The majority of the procedures related to nail enhancement are not performed by dermatologists but by beauticians with inadequate or no knowledge of the nail's anatomy and functions. The hygiene at the so-called nail-salons/beauty parlours is not standardized, leading to acute complications like paronychia and nail dystrophy following matrix injury. The use of nail cosmetics has become widespread, making it essential for dermatologists to be aware of the nail care products, aesthetic procedures pertaining to nails, and related adverse effects.
PubMed: 37317711
DOI: 10.25259/IJDVL_77_2023 -
Journal of Cutaneous and Aesthetic... 2022Paronychia refers to the inflammation of the tissue which immediately surrounds the nail and it can be acute (<6 weeks duration) or chronic (>6 weeks duration).... (Review)
Review
Paronychia refers to the inflammation of the tissue which immediately surrounds the nail and it can be acute (<6 weeks duration) or chronic (>6 weeks duration). Disruption of the protective barrier between the nail plate and the adjacent nail fold preceded by infectious or noninfectious etiologies results in the development of paronychia. A combination of general protective measures, and medical and/or surgical interventions are required for management. This review explores the pathogenesis, clinical features, differential diagnosis, medical, and surgical management of paronychia. For the purpose of this review, we searched the PubMed, Cochrane, and Scopus databases using the following keywords, titles, and medical subject headings (MeSH): acute paronychia, chronic paronychia, and paronychial surgeries. Relevant review articles, original articles, and case reports/series published till February 2020 were included in this study.
PubMed: 35655642
DOI: 10.4103/JCAS.JCAS_30_21