Neoadjuvant (Induction) Erlotinib Response in Stage IIIA Non–Small-Cell Lung Cancer

Kappers, Ingrid; Klomp, Houke M.; Burgers, Jacobus A.; Zandwijk, Nico van; Haas, Rick L.; Pel, Renée van

doi:10.1200/jco.2008.16.3709

Cited by 34 publications

(18 citation statements)

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“…Erlotinib is able to induce swift responses in selected NSCLC patients and prolongs survival when given as a second-line treatment in advanced disease (20,21). However, in many patients no objective response is achieved (22).…”

Section: Discussionmentioning

confidence: 99%

Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Aukema¹,

Kappers²,

Olmos³

et al. 2010

J Nucl Med

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Early prediction of treatment response is of value in avoiding the unnecessary toxicity of ineffective treatment. The objective of this study was to prospectively evaluate the role of integrated 18 F-FDG PET/CT for the early identification of response to neoadjuvant erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. Methods: From October 2006 to March 2009, 23 patients with non-small cell lung cancer eligible for surgical resection were evaluated for this study. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. 18 F-FDG PET/CT was performed before and at 1 wk after the administration of erlotinib. Changes in tumor 18 F-FDG uptake during treatment were measured by standardized uptake values and assessed prospectively according to the criteria of the European Organization for Research and Treatment of Cancer. Patients with a decrease in standardized uptake values of 25% or more after 1 wk were classified as "metabolic responders." The metabolic response was compared with the pathologic response, obtained by histopathologic examination of the resected specimen. Results: Following the 18 F-FDG PET/CT criteria of the European Organization for Research and Treatment of Cancer, 6 patients (26%) had a partial response within 1 wk, 16 patients (70%) had stable disease, and 1 patient (4%) had progressive disease. The median percentage of necrosis in the early metabolic responder group was 70% (interquartile range, 30%-91%), and the median percentage of necrosis in the nonresponder group was 40% (interquartile range, 20%-50%; P 5 0.09). The k-agreement between the metabolic and pathologic responders was 0.55 (P 5 0.008). Conclusion: The results of this study suggest that early during the course of epidermal growth factor receptor tyrosine kinase inhibitor therapy, 18 F-FDG PET/CT can predict response to erlotinib treatment in patients with non-small cell lung cancer.

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Section: Discussionmentioning

confidence: 99%

Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Aukema¹,

Kappers²,

Olmos³

et al. 2010

J Nucl Med

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“…[8]whodescribed2successfulcasesofpreoperative down-stagingofEGFRmutation-positiveNSCLCwithgefitinib,aswellastothecommunicationofKappersetal. [9]who provided a similar report on a patient treated with erlotinib. Ascomparedtotheabovepublications,ourpresentationisaccompaniedbyfollow-updata.Unfortunately,bothourpatients relapsed,however,thecircumstancesofthediseaserecurrence were different.…”

Section: Discussionmentioning

confidence: 95%

“…[8]andKappersetal. [9]demonstrateanewopportunityforthemanagementofpatientswithadvancedNSCLC,whosetumorscontainTKI-sensitizingmutations.However,somecriticalissues remain open. Most importantly, it has not yet been proven directly, whether good TKI responders indeed benefit from the resection of the residual tumor mass, or whether simple continuationofgefitiniborerlotinibtreatmentwouldprovide similarsurvivalevenwithoutsurgery.Inaddition,theabove presented cases describe patients with otherwise inoperable NSCLC; it remains to be clarified whether gefitinib or erlotinibhavetobeusedingenuineneoadjuvantsettings,i.e.for thepreoperativetreatmentoftheresectableEGFRmutationpositive disease.…”

Section: Discussionmentioning

confidence: 99%

Down-Staging of EGFR Mutation-Positive Advanced Lung Carcinoma with Gefitinib Followed by Surgical Intervention: Follow-Up of Two Cases

Levchenko

Moiseyenko²,

Matsko³

et al. 2009

Onkologie

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Background: Non-small cell lung carcinomas (NSCLC) carrying a mutation in the epidermal growth factor receptor (EGFR) gene show unprecedented sensitivity to gefitinib or erlotinib. Case Reports: We present the follow-up data of 2 EGFR mutation-positive stage IV NSCLC patients who received upfront 250 mg gefitinib daily, then underwent potentially curative surgery, and resumed gefitinib therapy in the adjuvant setting. Patient 1 was diagnosed with a rightsided adenocarcinoma of the upper lobe with multiple metastases to the middle lobe. After 2 months of gefitinib treatment, only a small primary lesion was seen, and a bilobectomy with lymph node dissection was performed. The patient remained disease-free during a scheduled 12-month adjuvant therapy but relapsed 9 weeks after cessation of this treatment. Patient 2 presented with adenocarcinoma of the lower lobe of the right lung and a single metastasis to the left adrenal. After 3 months of receiving gefitinib, the metastasis was no longer detectable, and the primary tumor was significantly reduced. Surgery included lobectomy and adrenalectomy. This patient relapsed with metastasis in the remaining adrenal 4 months after the start of adjuvant therapy. Conclusion: Gefitinib can be used preoperatively for the management of advanced EGFR mutation-positive NSCLC. It remains to be established whether surgical intervention indeed renders survival advantage for this category of patients.

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“…Neoadjuvant use of egfr-tkis has been reported only anecdotally so far. One case reported from the Netherlands involved a 67-year-old never-smoker with pet-staged iiia nsclc with an EGFR exon 19 deletion 8 . That patient was treated with preoperative erlotinib, resulting in a rapid and complete pathologic response.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Erlotinib and Surgical Resection of a Stage IIIA Papillary Adenocarcinoma of the Lung with an L861Q Activating EGFR Mutation

et al. 2012

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A 78-year-old Caucasian woman presented in August 2009 with progressive nonproductive cough for 5 months and dyspnea and fatigue for 2 weeks. Her symptoms were unresponsive to clarithromycin, and chest radiography revealed a large, ill-defined right lower lung opacity. Past medical, family, and occupational history were not contributory; she had smoked 1 pack-year until age 22. Functionally, she was independent and had been swimming daily until 2 months earlier, but she was now dyspneic walking on level ground (Medical Research Council Dyspnea Index grade 3 1 ). Physical examination revealed diminished breath sounds at the right base. There was no digital clubbing. Blood count and chemistry were normal. Eastern Cooperative Oncology Group (ecog) performance status (ps) was 1.Staging computed tomography (ct) demonstrated a 7.4×5.6-cm mass in the right middle lobe and a 12-mm pre-carinal lymph node. Bronchoscopy was normal, but transbronchial biopsies (Figure 1) revealed numerous large malignant cells with glandular papillary structures and micropapillae positive for ABSTRACTThe use of epidermal growth factor receptor tyrosine kinase inhibitors (egfr-tkis) is evolving, as is an understanding of predictive biomarkers for tumour response in non-small-cell lung cancer (nsclc). In this report, we describe a case of rapidly progressing, borderline-resectable, clinical stage iiia (micro) papillary adenocarcinoma in a 78-year-old woman who experienced a profound response to neoadjuvant erlotinib without short-term toxicity. On EGFR mutation testing, this patient had an uncommon activating point mutation at L861Q in exon 21. Her response permitted successful surgical resection with negative margins and avoidance of chemoradiation, which she was deemed too frail to tolerate. Our case addresses unique management issues such as preoperative testing for EGFR mutation, utility of histology in predicting EGFR mutations, and use of egfr-tkis pre-and postoperatively for potentially resectable nsclc.

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Neoadjuvant (Induction) Erlotinib Response in Stage IIIA Non–Small-Cell Lung Cancer

Abstract: ACKNOWLEDGMENTWe thank Renato Valdes Olmos, MD, PhD, nuclear medicine physician, and Jelle Teertstra, MD, radiologist, for their assistance in producing the [ 18 F]FDG-PET/CT scan and CT scan images for this report.

Cited by 34 publications

References 1 publication

Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Down-Staging of EGFR Mutation-Positive Advanced Lung Carcinoma with Gefitinib Followed by Surgical Intervention: Follow-Up of Two Cases

Neoadjuvant Erlotinib and Surgical Resection of a Stage IIIA Papillary Adenocarcinoma of the Lung with an L861Q Activating EGFR Mutation

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Neoadjuvant (Induction) Erlotinib Response in Stage IIIA Non–Small-Cell Lung Cancer

Abstract: ACKNOWLEDGMENTWe thank Renato Valdes Olmos, MD, PhD, nuclear medicine physician, and Jelle Teertstra, MD, radiologist, for their assistance in producing the [ 18 F]FDG-PET/CT scan and CT scan images for this report.

Cited by 34 publications

References 1 publication

Is 18F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Is 18F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Down-Staging of EGFR Mutation-Positive Advanced Lung Carcinoma with Gefitinib Followed by Surgical Intervention: Follow-Up of Two Cases

Neoadjuvant Erlotinib and Surgical Resection of a Stage IIIA Papillary Adenocarcinoma of the Lung with an L861Q Activating EGFR Mutation

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Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Is ¹⁸F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?