Four-Year Complete Remission in a Patient with Metastatic Epidermal Growth Factor Receptor–Mutated Lung Cancer Treated with Two Cycles of Erlotinib
Authors: Brendan McCann, Brian Clark
Journal: Journal of Thoracic Oncology (2017)

EGFR tyrosine kinase inhibitors (TKIs) are the optimal first-line treatment option for patients with metastatic EGFR-mutated adenocarcinoma of the lung, but they have also been used as second-line treatment for metastatic cancer of the lung. In April 2012 a 52-year-old woman was referred to hospital with fatigue and a cough. A computed tomography (CT) scan revealed collapse of the left upper lobe of the lung with a mass in the left perihilar and paramediastinal area. There were also two low-attenuation lesions present in the right lobe of the liver: one measuring 4.2 cm and the other measuring 1.4 cm (Fig. 1). Bronchoscopy confirmed a poorly differentiated adenocarcinoma. Her medical history included hypertension, gastroesophageal reflux, chronic kidney disease, and osteoarthritis, and she was an ex-smoker. She commenced four cycles of palliative chemotherapy with cisplatin, 75 mg/m2, and pemetrexed, 500 mg/m2, every 3 weeks. An end-of-treatment CT scan in September 2012 showed response, with the large liver metastasis reducing to 1.6 cm but continuing left upper lobe collapse (Fig. 2). Symptomatically, a cough developed, so the patient received 20 Gy in five fractions of palliative radiotherapy to the left upper lobe in September 2012. A CT scan in March 2013 suggested progressive liver disease, and an ultrasound scan confirmed the increasing size of the liver metastasis to 2 cm. The patient began receiving erlotinib (Tarceva, Genentech, South San Francisco, CA), 150 mg once a day, in March 2013 as part of second-line treatment. She was able to tolerate only two cycles on account of diarrhea. A CT scan in May 2013 showed resolution of the primary lesion, with no masses seen in the liver, and this was confirmed by ultrasonography. Retrospective analysis of her original bronchoscopy tissue sample confirmed detection of an EGFR sensitizing sequence variant, p.Leu747_Ser752del. Incredibly, despite no further intervention, there has been no recurrence of her metastatic lung adenocarcinoma as of July 2017 (Fig. 3). EGFR TKIs produce much greater response rates than standard chemotherapy in patients with EGRF mutations; however, in landmark phase III studies complete response is rare, with rates ranging from 0% to 2%.1Qi W.X. Fu S. Zhang Q. Guo X.M. Anti-epidermal-growth-factor-receptor agents and complete responses in the treatment of advanced non-small-cell lung cancer: a meta-analysis of 17 phase III randomized controlled trials.Curr Med Res Opin. 2015; 31: 25-33Crossref PubMed Scopus (11) Google Scholar There have been previous published case studies reporting complete response in patients with sustained response2Zhu Z. Chai Y. Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with icotinib.Thorac Cancer. 2016; 7: 681-683Crossref PubMed Scopus (4) Google Scholar, 3Vitale M.G. Riccardi F. Mocerino C. et al.Erlotinib-induced complete response in a patient with epidermal growth factor receptor wild-type lung.J Med Case Rep. 2014; 24: 102Crossref Scopus (2) Google Scholar; however, they have involved much shorter time scales and the patient received maintenance treatment, whereas our patient received only two cycles and had to stop treatment because of toxicity. However, as of the time of the writing of this letter, which is 4 years since the patient stopped receiving treatment or any further anticancer medication, she has not had any recurrence of her disease. Stopping EGFR TKIs if they have intolerable side effects may be a future treatment strategy in patients who obtain a complete response.