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Cancers Nov 2023This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and...
Real-World Treatment Outcomes and Safety of Afatinib in Advanced Squamous Cell Lung Cancer Progressed after Platinum-Based Doublet Chemotherapy and Immunotherapy (SPACE Study).
This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and immunotherapy. We recruited patients both retrospectively and prospectively and collected the outcomes and safety data. Additionally, we performed next-generation sequencing using tumor tissue and/or plasma to explore potential molecular biomarkers. Altogether, 42 patients were included in the final analysis. The median number of prior treatments was three (range 1-8), and the median TTF was 2.1 months. Objective response rate and disease control rate were 16.2% and 59.5%, respectively, and median duration of response was 4.0 months among response evaluable patients ( = 37). Treatment-related adverse events (TRAEs, including diarrhea, stomatitis, and paronychia) occurred in 22 (52.3%) patients; however, most were grade 2 or lower, and only 5 cases were grade 3. TRAEs led to dose modification in 17 (40.5%) and discontinuation in 4 (9.5%) patients. The TTF in patients with mutations was significantly longer than that in patients without (6.8 vs. 2.1 months, = 0.045). Our results highlight that afatinib is a reasonable treatment option in terms of effectiveness and safety, and mutation can be used as a predictive biomarker in clinical settings.
PubMed: 38067272
DOI: 10.3390/cancers15235568 -
Cancer Research and Treatment Apr 2024GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase...
PURPOSE
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
MATERIALS AND METHODS
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
RESULTS
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
CONCLUSION
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; ErbB Receptors; Fluorouracil; Irinotecan; Leucovorin; Neoplasm Recurrence, Local; Rectal Neoplasms
PubMed: 38062706
DOI: 10.4143/crt.2023.1117 -
JTO Clinical and Research Reports Dec 2023Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The...
A Phase 2 Single-Arm Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis NSCLC: Results for the First-Line Cohort of the OCEAN Study (LOGIK 1603/WJOG 9116L).
INTRODUCTION
Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with mutation. Here, we report the results of the first-line cohort.
METHODS
Previously untreated patients with RT-naive CNS metastasis and mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points.
RESULTS
A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%).
CONCLUSIONS
These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting.
TRIAL REGISTRATION
UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.
PubMed: 38046380
DOI: 10.1016/j.jtocrr.2023.100587 -
Cancers Oct 2023Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second...
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).
Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
PubMed: 37894366
DOI: 10.3390/cancers15204999 -
BMC Cancer Oct 2023About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to...
BACKGROUND
About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC.
METHODS
Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.
RESULT
Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs.
CONCLUSIONS
Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cohort Studies; Antineoplastic Agents; Protein Kinase Inhibitors; ErbB Receptors; Mutation
PubMed: 37840124
DOI: 10.1186/s12885-023-11465-2 -
Indian Dermatology Online Journal 2023
PubMed: 37727563
DOI: 10.4103/idoj.idoj_527_22 -
Cureus Sep 2023Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative,...
Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management. Methods This observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee. Results Among the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes. Conclusions Beyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.
PubMed: 37701161
DOI: 10.7759/cureus.45007 -
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 -
Skin Appendage Disorders Aug 2023Onychogryphosis is a nail condition characterized clinically by a thickened, curved, yellow-brown, and opaque nail plate and may result in pain, paronychia, and...
INTRODUCTION
Onychogryphosis is a nail condition characterized clinically by a thickened, curved, yellow-brown, and opaque nail plate and may result in pain, paronychia, and onychogryphosis.
METHODS
We performed a nested case-control study of 1,114 onychogryphosis patients and 3,423 matched controls to quantify the association between onychogryphosis and self-care limitations, chronic foot injury, dermatologic conditions, and vascular disease.
RESULTS AND CONCLUSION
Onychogryphosis was positively associated with increased age, activity limitations (difficulty running errands alone, bathing, and concentrating), psoriasis, onychomycosis, hallux malleus, hallux valgus, peripheral vascular disease, lower extremity ulcers, venous varices, and type II diabetes mellitus. Therefore, physicians should screen patients presenting with onychogryphosis for these conditions.
PubMed: 37564683
DOI: 10.1159/000530096