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

Abstract

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.

IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy

“…In addition, few case reports have also been reported. [101][102][103][104][105][106][107][108][109] Among the cohort studies, only one study included detailed assessment of the histopathologic parameters and molecular markers, and their correlation with radiologic responses. Several studies have noted in the tumors of patients who exhibited clinical response, the presence of extensive areas of fibrosis or necrosis with only focal residual tumor cells.…”

Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

“…In addition, EGFR TKI therapy in advanced stage NSCLC is a critical treatment with excellent tumor response and improvement of PFS [3,4,13,28]. Many clinical trials have assessed EGFR TKI as a neoadjuvant or adjuvant therapy in early stage NSCLC [14][15][16][17], while other reports used EGFR TKI as a neoadjuvant therapy followed by thoracic surgery in advanced stage NSCLC [21][22][23][24][25][26][27].…”

“…While thoracic surgery may possibly improve survival in advanced stage NSCLC patients and TKIs are a critical treatment for advanced stage EGFR-mutation positive NSCLC, the role of neoadjuvant TKI therapy followed by thoracic surgical resection in advanced stage EGFR-mutation positive NSCLC is still unclear. Several case reports failed to provide de nite prognosis [6, [21][22][23][24][25][26][27]. Our study investigated the possible impact of neoadjuvant TKI therapy, followed by thoracic surgery in advanced stage EGFR-mutation positive NSCLC patients.…”

Use of a tyrosine kinase inhibitor as neoadjuvant therapy for non-small cell lung cancer: A case report

“…No randomised phase III trials have been conducted in the neoadjuvant setting with gefitinib or erlotinib, but some favourable data already exist, most of which are in the form of case reports. 15–19 …”