Induction therapy with Erlotinib (E) and Gemcitabine/Platinum (GP) in stage III NSCLC
Published on: 28th January, 2021
OCLC Number/Unique Identifier: 8913463613
Background: In 2004 we started a phase II trial in non-small lung cancer (NSCLC), stage III, with erlotinib followed by a combination with a platinum-based doublet in unselected patients to identify molecular subgroups benefitting from an EGFR targeting approach.
Patients and methods: Induction with erlotinib (E, 150 mg, d1-42) was followed by three cycles of gemcitabine (G, 1250 mg/m², d1+d8, q3w) and cisplatin (P, 80 mg/m², d1, q3w). Patients with at least stable disease after E were treated with a GP + E combination. Induction was followed by surgery and radiation. The trial was conducted as a prospective, multi-center, open label, exploratory phase II study to determine pathological response rate (pRR), as well as secondary endpoints disease free survival (DFS) and overall survival (OS).
Results: Of 38 prescreened patients 16 were included in the main study. Due to slow recruitment the study had to be terminated early. Combination of E and GP was well tolerated, surgery was feasible after induction therapy in 12 of 16 patients, 7/12 (58%) patients had a major pathological response (MPR). Median overall survival for patients with MPR was 57.7 months (confidence interval (CI), 37.4 to 78.0; n = 7) and for patients without MPR 11.9 months (CI, 6.4 to 17.4; n = 5). 2/16 patients had an epidermal growth factor receptor (EGFR) mutation.
Conclusion: Before discovery of distinct molecular mechanisms in NSCLC our study was an attempt to identify clinical and pathological subgroups that would benefit from E induction. Two patients with an EGFR mutation were identified. MPR was a predictor of long term disease free and overall survival.
Molecular Mechanisms and Potential Predictive Biomarkers in Advanced Non-small Cell Lung Cancer: A Summary of Current and Future Trends
Published on: 27th June, 2024
Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.
Pulmonary Pleomorphic Carcinoma: A Rare Entity Revisited!
Published on: 4th June, 2025
Introduction: Pleomorphic Carcinoma (PC) is a subset of poorly differentiated non–small cell lung cancer that is diagnostically challenging because it is a rare malignancy of the lung. It shows varying dual-cell components; spindle or giant cells and epithelial cells.Method: We report a case of 68-year-old non-smoking female who presented with cough, fever, pain in the left side of chest & weight loss of recent onset and an abnormal shadow on her chest X-ray. Computed tomography of chest revealed a well defined heterogeneously enhancing cavitatory soft tissue lesion in the posterior basal segment of the left lower lobe with mediastinal lymphadenopathy.Results: Fine needle aspiration cytology& percutaneous lung biopsy confirmed poorly differentiated malignant tumor. Patient underwent a left lower lobectomy. A diagnosis of PC was confirmed after Immunohistochemistry (IHC). Mutation analysis revealed an EGFR exon 21 mutation within the tumor cells. The patient is on Gefitinib based chemotherapy and has remained disease-free for three years post-surgery.Conclusion: PC of the lung is a rare pathological entity. Definite diagnosis may only be made on a resected tumor along with the use of IHC. Surgical resection is the main modality of the treatment. Such rare cases should be documented to establish an optimal management plan and to provide a further insight to targeted therapy.
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