Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (original) (raw)
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Oncology Reports, 2013
Erlotinib is a reversible tyrosine kinase inhibitor of epidermal growth factor receptor (TKI EGFR). In Poland, as of July 2012, it is used in the treatment only of patients with non-small cell lung cancer (NSCLC) and with EGFR mutation gene after standard chemotherapy failure. The effectiveness of erlotinib in second-or third-line treatment of NSCLC patients without EGFR activating mutation gene remains debatable. Clinical trial results indicated that TKI EGFR showed an efficacy of 70-80% in patients with EGFR mutations, while the clinical response to treatment among unselected Caucasian patients is only 10%. The present study was conducted in a group of 71 patients with inoperable, locally advanced or metastatic NSCLC treated with erlotinib as the second-or third-line therapy. Molecular tests (examination of EGFR mutation and gene amplification) were carried out retrospectively. Objective response rate, overall survival (OS) and progression-free survival (PFS) were calculated. Effects of clinical and molecular factors including the presence of EGFR mutations, EGFR gene amplification, patient performance status, rash, smoking status, time from diagnosis to start of therapy, weight loss and the serum LDH levels were analyzed. An objective response in the form of partial response occurred in only 5 patients (7%), who carried EGFR gene mutation. Median time to PFS for the entire group of patients was 1.5 months and median OS was 10 months. The strongest factors increasing the risk of progression in patients treated with erlotinib were the absence of activating mutations in the EGFR gene (6-fold increased risk) and no treatment-related rash (4.5-fold increased risk). The most important factors affecting the risk of early mortality were poor performance status (HR 37.344; P>0.0001), no treatment-related rash (HR 14.9348; P= 0.0002) and a short response time on the first-line chemotherapy (HR 9.519; P= 0.0445).
Journal of Thoracic Oncology, 2010
Backgrounds: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in Asian patients with non-small cell lung cancer. Recently, the survival advantage of erlotinib, another tyrosine kinase inhibitor, was not affected by EGFR mutation status in a phase III trial, indicating that patients with EGFR-wild-type (EGFR-wt) tumors might also benefit from this tyrosine kinase inhibitor. The aim of this trial was to evaluate the efficacy and toxicity of erlotinib in Japanese patients with EGFR-wt tumors. Methods: The primary end point was an objective response. Patients with EGFR-wt tumors previously receiving one to three chemotherapy regimens were enrolled in this trial. The mutation status was assessed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Erlotinib was administered (150 mg/d) until disease progression or unacceptable toxicities occurred. Results: Thirty patients were enrolled between January and December 2008. Objective response was observed in one patient (3.3%), and the disease became stable in 18 patients (60.0%). Skin rash was the most common side effect. Grades 3-4 adverse events included pulmonary embolism, keratitis, and anemia. Two other patients developed interstitial lung disease (grades 1 and 2). Nevertheless, all these events were reversible, resulting in no treatment-related deaths. With a median follow-up time of 10.7 months, the median survival time and median progression-free survival times were 9.2 and 2.1 months, respectively. Conclusion: This is the first prospective biomarker study showing that erlotinib therapy for pretreated patients with EGFR-wt tumors seems to have a modest activity with no irreversible toxicity.
Frontiers in Oncology, 2019
Introduction: Mesenchymal epidermal transition and vascular endothelial growth factor pathways are important in mediating non-small cell lung cancer (NSCLC) tumorigenesis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance. We hypothesized that treatment with cabozantinib plus erlotinib in EGFR mutation-positive NSCLC following progression on EGFR TKI therapy may allow tumors to overcome this resistance or restore sensitivity to therapy regardless of T790M status. Methods: Patients with advanced NSCLC, known EGFR mutation and progressive disease on an EGFR TKI immediately prior to enrollment without intervening therapy were enrolled. Patients received erlotinib 150 mg and cabozantinib 40 mg daily. The primary endpoint was evaluation of efficacy by objective response rate. Secondary endpoints included assessment of progression free survival (PFS), overall survival, change in tumor growth rate, safety and toxicity, and the evaluation of specific EGFR mutations and MET amplification in pre-treatment tissue and plasma. Results: Thirty-seven patients were enrolled at 4 centers. Four patients had partial response (10.8%) and 21 had stable disease (59.5%). A greater than 30% increase in tumor doubling time was observed in 79% of assessable patients (27/34). Median PFS was 3.6 months for all patients. Diarrhea (32%) was the most common grade 3 adverse event; 3 patients had asymptomatic grade 4 elevation of amylase and lipase. Reckamp et al. Cabozantinib and Erlotinib in EGFR NSCLC Conclusions: Combination erlotinib and cabozantinib demonstrates activity in a highly pretreated population of patients with EGFR mutation and progression on EGFR TKI. Further elucidation of beneficial patient subsets is warranted.
Chinese clinical oncology, 2016
Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation. Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0-3 were included in this study. Low-dose erlotinib (25 mg/day) was administered until disease progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), OS, and safety. The required sample size was 40 patients. The study was stopped early, after achieving only 28% of planned enrollment, due to poo...
Oncology Letters, 2017
Erlotinib is one of the treatment choices for patients with advanced non-small cell lung cancer (NSCLC), regardless of the epidermal growth factor receptor (EGFR) mutation status. However, its efficacy for the treatment of patients with NSCLC with EGFR wild type or who are beyond the usage of gefitinib remains controversial. The present study therefore retrospectively assessed the efficacy of erlotinib in patients with wild type EGFR who had previously undergone gefitinib therapy. A total of 222 patients with NSCLC who received chemotherapeutic treatment with erlotinib between July 2007 and February 2013 were evaluated. The background variables, response rates, progression-free survival (PFS) and overall survival rates were retrospectively analyzed. The male/female ratio of patients was 103/119, and patients had a median age of 63 years (range, 33-95 years). A total of 10 of the 222 patients had clinical stages IIIB/IV, 191 had adenocarcinoma, 5 had large cell carcinoma, 10 had squamous cell carcinoma and 6 had NSCLC of a variety not otherwise specified. The EGFR mutation was positive, wild type or unknown in 95, 52 and 75 patients, respectively. In the 52 patients with EGFR wild type, there were 3 partial responders, 25 with stable disease and 24 with progressive disease, for a response rate of 6% [95% confidence interval (CI), 1.3-15%]. The median PFS of EGFR wild type and positive were 1.1 months (95% CI, 1.04-1.16 months) and 5.42 months (95% CI, 5.43-5.68 months), respectively. The results of the study demonstrated that erlotinib is not sufficiently effective for patients with NSCLC who possess the EGFR wild type status.