Erlotinib in Metastatic Bronchopulmonary Mucoepidermoid Carcinoma

Bronchopulmonary mucoepidermoid carcinoma (MEC) accounts for less than 1% of lung tumors. All age groups are affected, but 50% of these cases occur in patients younger than 30 years. Chemotherapy has demonstrated limited success in treating this rare condition. Responses to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has been reported in patients with recurrent metastatic bronchopulmonary MEC.1Han SW Kim AP Jeon YK et al.Mucoepidermoid carcinoma of lung: potential target of EGFR-directed treatment.Lung Cancer. 2008; 61: 30-34Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 2Rossi G Sartori G Cavazza A et al.Mucoepidermoid carcinoma of the lung, response to EGFR inhibitors, EGFR and K-RAS mutations, and differential diagnosis.Lung Cancer. 2008; 63: 159-160Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar We report a case of bronchopulmonary MEC responding to treatment using the EGFR TKI, erlotinib. A 35-year-old Chinese male patient presented with a mediastinal tumor with no nodal or distant metastases on positron emission tomography-computed tomography (CT) scan. He received excision of the anterior mediastinal tumor with en-bloc wedge resection of the bilateral upper lobes of lung (Figure 1). Pathological review showed a 5 cm × 12 cm × 11 cm, high-grade MEC, with no nodal involvement. He received adjuvant radiotherapy for involved adventitial margins. Inoperable local recurrence with superior vena cava (SVC) obstruction was detected by contrast CT scan 1 year later. He declined systemic treatment for 4 months from diagnosis but received SVC stent insertion and pacemaker insertion for complete heart block and congestive heart failure secondary to malignant tumor infiltration of bilateral atria and right ventricular outflow tract. A contrast CT scan at 4 months from recurrence showed occlusion of the SVC stent, pericardial effusion, bilateral lung and pleural metastases, left pleural effusion, and splenic metastasis. Erlotinib was initiated empirically, without EGFR mutational analysis. A chest radiograph taken 2 weeks after treatment initiation showed disease response. The patient experienced complications of grade 3 acneiform rash, grade 2 hand-foot syndrome, and warfarin overdose upon clinical review at 4 weeks. Therapeutic level of anticoagulation was achieved by dose reduction in warfarin, and the skin complications were managed by topical therapy. A contrast CT scan at 6 weeks of treatment showed at least partial response in all disease sites (Figure 2). The patient presented with prehospital cardiac arrest 8 weeks after treatment. A retrospective analysis of the EGFR mutational status by direct sequencing performed on the resected surgical specimen was negative. This is the third case report that has demonstrated clinical responses of bronchopulmonary MEC to EGFR TKI in the absence of a sensitizing EGFR mutation. 30 to 40% of patients with EGFR wild-type non-small cell lung cancer (NSCLC) develop stable disease after EGFR TKI therapy. Two phase III trials examining erlotinib in EGFR wild-type NSCLC has demonstrated improved survival when compared with placebo.3Cappuzzo F Ciuleanu T Stelmakh L et al.Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomized, placebo-controlled phase 3 study.Lancet Oncol. 2010; 11: 521-529Abstract Full Text Full Text PDF PubMed Scopus (1145) Google Scholar, 4Tsao MS Sakurada A Cutz JC et al.Erlotinib in lung cancer—molecular and clinical predictors of outcome.N Engl J Med. 2005; 353: 133-144Crossref PubMed Scopus (1738) Google Scholar In vitro studies employing salivary MEC and NSCLC cell lines have shown that 38 to 81% of salivary MECs harbor a t(11;19) translocation resulting in the CRTC1-MAML2 fusion oncogene. This fusion protein is also present in bronchopulmonary MEC and induces a >20-fold expression in amphiregulin.5O'Neill ID Gefitinib as targeted therapy for mucoepidermoid carcinoma of the lung: possible significance of CRTC1–MAML2 oncogene.Lung Cancer. 2009; 64: 129-130Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Amphiregulin upregulation predicts tumor growth inhibition by gefitinib in EGFR wild-type NSCLC cell lines in vitro. Subject to further investigations in the clinical setting, CRTC-MAML2 oncogene may be a feasible target for EGFR TKI therapy, expanding the scope of treatment with these agents beyond EGFR-sensitizing mutations.