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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 -
The New England Journal of Medicine Apr 2020No approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.
BACKGROUND
No approved therapies exist for inoperable plexiform neurofibromas in patients with neurofibromatosis type 1.
METHODS
We conducted an open-label, phase 2 trial of selumetinib to determine the objective response rate among patients with plexiform neurofibromas and to assess clinical benefit. Children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas received oral selumetinib twice daily at a dose of 25 mg per square meter of body-surface area on a continuous dosing schedule (28-day cycles). Volumetric magnetic resonance imaging and clinical outcome assessments (pain, quality of life, disfigurement, and function) were performed at least every four cycles. Children rated tumor pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable).
RESULTS
A total of 50 children (median age, 10.2 years; range, 3.5 to 17.4) were enrolled from August 2015 through August 2016. The most frequent neurofibroma-related symptoms were disfigurement (44 patients), motor dysfunction (33), and pain (26). A total of 35 patients (70%) had a confirmed partial response as of March 29, 2019, and 28 of these patients had a durable response (lasting ≥1 year). After 1 year of treatment, the mean decrease in child-reported tumor pain-intensity scores was 2 points, considered a clinically meaningful improvement. In addition, clinically meaningful improvements were seen in child-reported and parent-reported interference of pain in daily functioning (38% and 50%, respectively) and overall health-related quality of life (48% and 58%, respectively) as well as in functional outcomes of strength (56% of patients) and range of motion (38% of patients). Five patients discontinued treatment because of toxic effects possibly related to selumetinib, and 6 patients had disease progression. The most frequent toxic effects were nausea, vomiting, or diarrhea; an asymptomatic increase in the creatine phosphokinase level; acneiform rash; and paronychia.
CONCLUSIONS
In this phase 2 trial, most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas had durable tumor shrinkage and clinical benefit from selumetinib. (Funded by the Intramural Research Program of the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803.).
Topics: Adolescent; Benzimidazoles; Child; Child, Preschool; Female; Humans; Male; Mitogen-Activated Protein Kinase Kinases; Nausea; Neurofibroma, Plexiform; Neurofibromatosis 1; Pain; Patient Reported Outcome Measures; Progression-Free Survival; Protein Kinase Inhibitors; Tumor Burden
PubMed: 32187457
DOI: 10.1056/NEJMoa1912735 -
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 -
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 -
The Orthopedic Clinics of North America Apr 2024The fingertip is the interface between humans and the world, including the various thorns, dirty needles, and other hazards to be found there. It is unsurprising that... (Review)
Review
The fingertip is the interface between humans and the world, including the various thorns, dirty needles, and other hazards to be found there. It is unsurprising that this is the site where hand infections most frequently occur. Although commonly encountered by hand surgeons and other physicians, fingertip infections have several mimics, and diagnosis and management is not always straightforward. Early diagnosis and treatment are key to success. As with all infections, they are more common and are more aggressive in immunosuppressed patients. This article reviews fingertip anatomy, common and uncommon fingertip infections and their mimics, and recommendations for management.
Topics: Humans; Fingers; Hand
PubMed: 38403372
DOI: 10.1016/j.ocl.2023.10.003 -
Journal of the American Podiatric... May 2020Retronychia is an uncommonly reported condition among the category of nail pathologies. It often presents mimicking similar nail disorders, such as onychocryptosis,... (Review)
Review
Retronychia is an uncommonly reported condition among the category of nail pathologies. It often presents mimicking similar nail disorders, such as onychocryptosis, onychomycosis, and paronychia. This pathologic condition has recently seen an increased presence in the literature, mainly in the form of case studies. Literature on retronychia was collected using PubMed, the US National Library of Medicine, the National Institutes of Health's online database, life science journals, and online books. References cited by these articles were also reviewed for additional relevant publications. Reviews, case studies, and retrospective articles were compiled and analyzed for commonalities in cause, patient demographics, clinical signs, and treatment. Retronychia may be more common than previously suggested. Proper knowledge and education of this pathologic nail condition is important to health-care professionals to achieve early and correct diagnosis.
Topics: Humans; Nail Diseases; Nails; Nails, Ingrown; Paronychia; Retrospective Studies; United States
PubMed: 32730608
DOI: 10.7547/17-155 -
Lung Cancer (Amsterdam, Netherlands) Nov 2022The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are...
Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: towards a proactive, multidisciplinary approach.
CONTEXTE
The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed. Amivantamab is a bispecific anti-EGFR and anti-MET antibody with expected skin toxicities.
OBJECTIVE
We developed here guidelines for prevention and treatment of cutaneous toxicities under amivantamab according to our experience at Institut Curie.
MATERIEL & METHOD
The first patients with metastatic lung cancer harboring EGFR Exon20ins mutation, included in the phase 1 CHRYSALIS trial and cured at Institute Curie from November 1st 2019 until December 31st 2021 were selected for this work. Retrospectively, all cutaneous adverse events were registered and classified according to the CTCAE 6.0 classification, and actions we implemented to minimize and treat these adverse events were collected. We then developed guidelines based on these datas.
RESULTS
A total of seven patients started amivantamab as monotherapy. The two most frequent dermatological adverse events were: acneiform rash and paronychia (100 % of patients). Other adverse events presented by the patients were reported: modification of hair growth with hypertrichosis in 50 % of men (n = 1/2) and hirsutism in 80 % of women (n = 4/5); skin abrasion of the scalp in 71 % (n = 5/7); and skin fissure in 57 % (n = 4/7). We recommend first a rigorous inspection of the skin and teguments to determine the risk rate to have dryer skin under treatment; second a prevention of paronychia/acneiform rash/and skin fissures with prophylactic tetracycline, skin moisturizing, and hygienic measures starting at least 14 days before treatment initiation; third a particular attention to the psychological impact of skin toxicities with access to psychological support.
CONCLUSION
We propose here guidelines for the management of dermatological toxicities under amivantamab with a multidisciplinary approach for the proactive management of cutaneous toxicities with a focus on preventive actions.
Topics: Female; Humans; Male; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Exanthema; Lung Neoplasms; Mutation; Paronychia; Protein Kinase Inhibitors; Skin Diseases
PubMed: 36198244
DOI: 10.1016/j.lungcan.2022.09.012