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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 -
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 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 -
Supportive Care in Cancer : Official... Aug 2011Epidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention... (Review)
Review
BACKGROUND
Epidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities.
METHODS
A multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities.
RESULTS
Prophylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible.
CONCLUSION
Prevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients' health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies.
Topics: Antineoplastic Agents; ErbB Receptors; Exanthema; Humans; Internationality; Practice Guidelines as Topic; Pruritus; Skin Diseases
PubMed: 21630130
DOI: 10.1007/s00520-011-1197-6 -
Presse Medicale (Paris, France : 1983) Nov 2014Paronychia is an inflammation of the folds of tissue surrounding the nail; proximal and/or lateral nail folds. Acute paronychia is mainly due to bacterial infection,... (Review)
Review
Paronychia is an inflammation of the folds of tissue surrounding the nail; proximal and/or lateral nail folds. Acute paronychia is mainly due to bacterial infection, Staphyloccus aureus or Streptococcus sometimes viral infection (herpetic whitlow). Chronic paronychia is the result of numerous conditions in which the main factor is the disappearance of the cuticle. On fingers, etiology is often a contact dermatitis; bacterial or mycological infections are secondary colonizations. Onychomycosis due to moulds (Fusarium) or dematiae (Scytalidium dimitiadum) are often associated with paronychia. Paronychia is a frequent side-effect of chemotherapies and targeted therapies. Paronychia is a common complication of lateral or proximal (retronychia) ingrown nail and systemic antibiotics are ineffective unless infection is proved. Do not use systematically systemic antibiotics.
Topics: Acute Disease; Chronic Disease; Drug-Related Side Effects and Adverse Reactions; Humans; Inflammation; Nails, Ingrown; Neoplasms; Paraneoplastic Syndromes; Paronychia; Skin Diseases
PubMed: 25441843
DOI: 10.1016/j.lpm.2014.06.009