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Journal of Clinical Oncology : Official... Oct 2021Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine...
PURPOSE
Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.
METHODS
CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5.
RESULTS
In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively.
CONCLUSION
Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with Exon20ins mutations after progression on platinum-based chemotherapy.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bispecific; Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Diarrhea; Disease Progression; Drug Eruptions; ErbB Receptors; Exons; Female; Humans; Hypokalemia; Injection Site Reaction; Lung Neoplasms; Male; Middle Aged; Mutagenesis, Insertional; Neutropenia; Organoplatinum Compounds; Paronychia; Progression-Free Survival; Pulmonary Embolism; Retreatment
PubMed: 34339292
DOI: 10.1200/JCO.21.00662 -
American Family Physician Jul 2017Paronychia is inflammation of the fingers or toes in one or more of the three nail folds. Acute paronychia is caused by polymicrobial infections after the protective... (Review)
Review
Paronychia is inflammation of the fingers or toes in one or more of the three nail folds. Acute paronychia is caused by polymicrobial infections after the protective nail barrier has been breached. Treatment consists of warm soaks with or without Burow solution or 1% acetic acid. Topical antibiotics should be used with or without topical steroids when simple soaks do not relieve the inflammation. The presence of an abscess should be determined, which mandates drainage. There are a variety of options for drainage, ranging from instrumentation with a hypodermic needle to a wide incision with a scalpel. Oral antibiotics are usually not needed if adequate drainage is achieved unless the patient is immunocompromised or a severe infection is present. Therapy is based on the most likely pathogens and local resistance patterns. Chronic paronychia is characterized by symptoms of at least six weeks' duration and represents an irritant dermatitis to the breached nail barrier. Common irritants include acids, alkalis, and other chemicals used by housekeepers, dishwashers, bartenders, florists, bakers, and swimmers. Treatment is aimed at stopping the source of irritation while treating the inflammation with topical steroids or calcineurin inhibitors. More aggressive techniques may be required to restore the protective nail barrier. Treatment may take weeks to months. Patient education is paramount to reduce the recurrence of acute and chronic paronychia.
Topics: Acute Disease; Chronic Disease; Diagnosis, Differential; Humans; Paronychia
PubMed: 28671378
DOI: No ID Found -
Annals of Medicine Dec 2022Nail conditions are not only aesthetic concerns, and nail changes may be a clue to an underlying systemic diseases or infection. Without timely treatment, nail diseases... (Review)
Review
Nail conditions are not only aesthetic concerns, and nail changes may be a clue to an underlying systemic diseases or infection. Without timely treatment, nail diseases can continue to worsen and significantly impair performance of daily activities and reduce quality of life. Examination of the nails is essential at every medical visit, and may uncover important findings. Brittle nail syndrome, onychomycosis, paronychia, nail psoriasis, longitudinal melanonychia, Beau's lines, onychomadesis and retronychia are common nail disorders seen in clinical practice. These conditions stem from infectious, inflammatory, neoplastic and traumatic aetiologies. Though each nail condition presents with its own distinct characteristics, the clinical findings may overlap between different conditions, resulting in misdiagnosis and treatment delays. Patients can present with nail plate changes (e.g. hyperkeratosis, onycholysis, pitting), discolouration, pain and inflammation. The diagnostic work-up of nail disease should include a detailed history and clinical examination of all 20 nail units. Dermoscopy, diagnostic imaging and histopathologic and mycological analyses may be necessary for diagnosis. Nail findings concerning for malignancy should be promptly referred to a dermatologist for evaluation and biopsy. Nail disease management requires a targeted treatment approach. Treatments include topical and/or systemic medications, discontinuation of offending drugs or surgical intervention, depending on the condition. Patient education on proper nail care and techniques to minimize further damage to the affected nails is also important. This article serves to enhance familiarity of the most common nail disorders seen in clinical practice. It will highlight the key clinical manifestations, systematic approaches to diagnosis and treatment options for each nail condition to improve diagnosis and management of nail diseases, as well as patient outcomes.Key messagesNail disease is not only a cosmetic issue, as nail changes can indicate the presence of a serious underlying systemic disease, infection or malignancy.Nail pain and changes associated with NP are physically and emotionally distressing and may contribute to functional impairment and diminished quality of life.LM is a hallmark sign of subungual melanoma and this finding warrants further investigation to rule out malignancy.
Topics: Humans; Nail Diseases; Nails; Neoplasms; Psoriasis; Quality of Life
PubMed: 35238267
DOI: 10.1080/07853890.2022.2044511 -
Clinics in Dermatology 2020Cutaneous leishmaniasis (CL) is called "the great imitator," because it can mimic almost all types of dermatoses. This similarity may sometimes lead to misdiagnosis,... (Review)
Review
Cutaneous leishmaniasis (CL) is called "the great imitator," because it can mimic almost all types of dermatoses. This similarity may sometimes lead to misdiagnosis, resulting in inappropriate treatment and morbidities. Atypical forms occur due to the interaction between parasitic factors and the host immune response. Secondary infection or mistreatment of CL can also alter the natural course, resulting in bizarre and misdiagnosed cases. Atypical leishmaniasis should be considered in longstanding and painless lesions that may simulate erysipelas, dermatitis, verruca, herpes zoster, paronychia, and sporotrichosis. Less commonly, sarcoidosis, deep mycosis, basal and squamous cell carcinoma, cutaneous lymphoma, or pseudolymphomalike lesions may need to be considered in the differential diagnosis. A high index of suspicion is required to consider a diagnosis of CL, especially in nonendemic or newly endemic regions. Smear, histopathologic examination, culture, and polymerase chain reaction serve as important tools to differentiate CL from its clinical and histologic look-alikes. CL is discussed from various perspectives, with emphasis on CL and its broad differential diagnosis.
Topics: Diagnosis, Differential; Diagnostic Errors; Diagnostic Techniques and Procedures; Humans; Leishmania; Leishmaniasis, Cutaneous; Polymerase Chain Reaction; Skin
PubMed: 32513395
DOI: 10.1016/j.clindermatol.2019.10.008 -
American Journal of Clinical Dermatology Oct 2018Coagulase-negative staphylococcus organisms may be normal flora of human skin, however these bacteria can also be pathogens in skin and soft tissue infections. A summary... (Review)
Review
Coagulase-negative staphylococcus organisms may be normal flora of human skin, however these bacteria can also be pathogens in skin and soft tissue infections. A summary of skin and soft tissue infections caused by coagulase-negative staphylococcus species is provided in this review. We conducted a search of the PubMed database using the following terms: abscess, auricularis, biofilm, capitis, cellulitis, coagulase, contaminant, cyst, draining, epidermidis, felon, folliculitis, furuncle, haemolyticus, hominis, indolent, infection, lugdunensis, mecA, microbiome, negative, osteomyelitis, paronychia, saprophyticus, skin, simulans, sinus, soft, staphylococcus, systemic, tissue, virulence, virulent, and vulvar. The relevant papers, and their references, generated by the search were reviewed. Skin and soft tissue infections have been observed to be caused by many coagulase-negative staphylococcus organisms: Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, and Staphylococcus simulans. Coagulase-negative staphylococcus skin infections predominantly present as abscesses and paronychia. They are most common in elderly patients or those individuals who are immunosuppressed, and tend to be broadly susceptible to antibiotic treatment. In conclusion, albeit less common, coagulase-negative staphylococcus organisms can result in skin and soft tissue infections, particularly in older and/or immunocompromised individuals. A review of the literature found that coagulase-negative staphylococcus organisms are most commonly grown in cultures of abscesses and paronychia. Therefore, coagulase-negative staphylococcal organisms should not always be considered as contaminants or normal flora, but rather as causative pathogens. They are usually susceptible to antibiotics used to treat methicillin-sensitive Staphylococcus aureus.
Topics: Abscess; Anti-Bacterial Agents; Coagulase; Humans; Immunocompromised Host; Paronychia; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus; Treatment Outcome
PubMed: 29882122
DOI: 10.1007/s40257-018-0362-9 -
Annals of Oncology : Official Journal... Jan 2018Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations... (Review)
Review
Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.
Topics: Acneiform Eruptions; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Chemical and Drug Induced Liver Injury; Diarrhea; Drug Resistance, Neoplasm; ErbB Receptors; Erlotinib Hydrochloride; Exons; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Molecular Targeted Therapy; Mucositis; Paronychia; Patient Selection; Progression-Free Survival; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 29462253
DOI: 10.1093/annonc/mdx702 -
American Journal of Clinical Dermatology Nov 2018Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in... (Review)
Review
Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25-85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients' quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.
Topics: Antineoplastic Agents; Dermatology; Drug Eruptions; Hair; Humans; Immunotherapy; Interdisciplinary Communication; Medical Oncology; Molecular Targeted Therapy; Mouth Mucosa; Nails; Neoplasms; Quality of Life; Skin; Treatment Outcome
PubMed: 30374901
DOI: 10.1007/s40257-018-0384-3 -
Hand Clinics Aug 2020The fingertip is the most common site of infections in the hand, which frequently are encountered by surgeons, dermatologists, and emergency and primary providers. Their... (Review)
Review
The fingertip is the most common site of infections in the hand, which frequently are encountered by surgeons, dermatologists, and emergency and primary providers. Their mismanagement may have serious consequences. This review discusses the unique anatomy of the volar fingertip pulp and perionychium and reviews pathophysiology and treatment of acute and chronic paronychia, including the decision for surgical versus medical management, choice of antibiotics, incisional techniques, and postincisional care. Felons and the evidence regarding their management are reviewed. Several infectious, rheumatologic, and oncologic conditions that may mimic common fingertip infections and about which the managing provider must be aware are presented.
Topics: Abscess; Anti-Bacterial Agents; Calcinosis; Diagnosis, Differential; Drainage; Fingers; Gout; Herpes Simplex; Humans; Neoplasms; Paronychia; Periarthritis; Skin Care; Soft Tissue Infections; Tendinopathy; Therapeutic Irrigation
PubMed: 32586457
DOI: 10.1016/j.hcl.2020.03.004