Durable complete remission of poor performance status metastatic lung adenocarcinoma patient treated with second-line erlotinib: a case report (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).
Advanced lung adenocarcinoma in an EGFR-positive patient treated with Erlotinib for 52 months
Respiratory Medicine Case Reports, 2013
The authors present a case of a 53-years-old non-smoker Caucasian female who was diagnosed with lung adenocarcinoma (stage IA) and underwent surgical resection in 2002. Five years later, the tumor relapsed (stage IV disease) and she initiated chemotherapy with carboplatin, gemcitabine and bevacizumab as a first-line therapy. Despite partial remission after four cycles, this regimen was discontinued due to unacceptable toxicity. In 2008, the disease progressed and the patient was started on Erlotinib as secondline treatment. The patient had a sustained partial remission which she maintains at present e 52 months after initiation of Erlotinib. Molecular testing performed on the primary lung tumor revealed an Epidermal Growth Factor Receptor (EGFR) gene mutation (deletion in exon 19).
Cancer Biology & Therapy, 2016
Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5-15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3 months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.
Retreatment with erlotinib of a patient with metastatic NSCLC harboring EGFR mutation: a case report
Tumori
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used for the treatment of advanced stage non-small cell lung cancer (NSCLC). Clinical trials have shown high efficacy of erlotinib, particularly in patients harboring activating mutations in the EGFR gene. Here we describe the case of a 42-year-old female light smoker diagnosed with EGFR mutation-positive adenocarcinoma of the left lung with pleural metastases, pleural effusion and metastases to the thoracic vertebrae (stage IV, T4NXM1). Although the patient developed resistance to erlotinib in the first line, she achieved disease stabilization lasting for 13 months as a response to erlotinib retreatment after 6 cycles of second-line chemotherapy. In conclusion, retreatment with erlotinib in our patient was effective. Therefore it should be considered as a good treatment option for patients with NSCLC harboring EGFR mutation.
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.
Anticancer Research, 2019
Aim: To assess the patterns of disease progression in advanced/metastatic epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) on first-line treatment with erlotinib and identify potential prognostic factors for progression-free survival (PFS). Patients and Methods: Patients with stage IIIB/IV EGFR-mutation-positive NSCLC receiving first-line erlotinib were followed-up until 24 months after the last patient was enrolled or until premature withdrawal for any cause. Results: A total of 127 evaluable patients were enrolled. The median PFS and overall survival were 8.8 and 19.1 months, respectively. Disease progression was asymptomatic in 57.6% of patients and 53.3% developed new sites of metastasis. The presence of liver metastasis was identified as an independent prognostic factor for poor PFS. Conclusion: Metastatic progression with asymptomatic disease seems to be the predominant pattern of disease progression on first-line erlotinib in real-life practice in patients with advanced/metastatic EGFR-mutant NSCLC. Additionally, the presence of liver metastases may negatively affect PFS in these patients. Non-small-cell lung cancer (NSCLC), accounting for more than 85% of lung cancer cases, is the leading cause of cancer-related death worldwide (1). Most patients with NSCLC present with locally advanced or metastatic disease at initial diagnosis (1). The standard first-line treatment has traditionally consisted of platinum-based combination chemotherapy, but unfortunately, it provides a modest overall survival (OS) benefit (2-4). Increased knowledge of the molecular biology of lung cancer has shifted the treatment paradigm towards individualized therapy based on molecular characterization of the tumor. Accordingly, epidermal growth factor receptor (EGFR) has become an important molecular target in NSCLC, and has led to the development of tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, afatinib, and the third-generation TKI osimertinib. The presence of EGFRactivating mutations has been associated with a superior clinical benefit of EGFR-TKIs in patients with advanced NSCLC (5-8). Compared to standard first-line platinumbased chemotherapy, treatment with EGFR-TKIs has shown a significantly improved clinical outcome in patients harboring activating mutations in exons 18-21 which encode the tyrosine-kinase domain of the EGFR gene (5-10). EGFR-TKI therapy has, therefore, emerged as the standard of care in the first-line setting for patients with NSCLC and EGFRactivating mutations.
Lung Cancer, 2014
Objectives: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are particularly effective in non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations. However, some studies have reported survival benefits in NSCLC patients with wild-type EGFR upon erlotinib treatment. This trial was conducted to evaluate the efficacy of erlotinib monotherapy and investigate the predictive values of several biomarkers. Patients and methods: Patients with previously treated NSCLC but without EGFR gene mutations that had never or light smoked were eligible for this study. Gene status screening was performed using the PNA-LNA PCR clamp method. Erlotinib was administered until disease progression or unacceptable toxicities occurred. EGFR gene status was re-evaluated using the fragment method to detect exon 19 deletions and the Cycleave-PCR method to detect point mutations. Expression of hepatocyte growth factor (HGF), Met, and thymidylate synthase (TS) were evaluated using immunohistochemistry. Results: Forty-seven patients were enrolled in the study between March 2010 and November 2011. Objective response rate (ORR) and disease control rate (DCR) were 15.2% and 41.3%. Re-evaluations for EGFR gene were performed in 32 tumor samples. EGFR gene mutations were found in eight samples (5:exon 19 deletion, 2:G719X, 1:L858R). Six patients had PR and two had SD among these eight patients. A total of 24 patients were confirmed as wild-type EGFR using different methods. ORR and DCR were 4.2% and 41.7%. The median progression free survival (PFS) and median survival times were 2.0 and 6.0 months, respectively. Patients with tumors expressing HGF showed shorter PFS but not MET or TS.