1. Authors: Syed H. Jafri ¹, Angel I. Blanco¹, Bonnie A. Labdi², Shan Guo¹. UT Houston department of medicine, Division of Oncology Department of Pharmacy Services, Memorial Hermann-Texas Medical Center Response to Erlotinib in Metastatic Lung Adenocarcinoma with a Rare Double Epidermal Growth Factor Receptor (EGFR) Mutation Introduction: Erlotinib is an EGFR tyrosine kinase inhibitor (TKI) which is approved as a first line treatment in patients with metastatic lung cancer with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Here we are reporting use of erlotinib in a patient with a rare double EGFR mutation. Case history: Patient is a 52 years old Hispanic female with PMH of reflux and 12 packs/year history of smoking who quit few years prior to diagnosis. She was evaluated for gradually worsening vision of one year duration and regular headaches for one month. MRI brain showed a 2 cm cystic lesion in right posterior temporal /parietal region. She underwent surgical resection which showed metastatic adenocarcinoma cells positive for CAM 5.2, CK 7, napsin and TTF-1 and negative for CK 20 consistent with lung primary. Staging PET/CT scan showed increased FDG uptake in a left upper lobe 2.5 cm perihilar mass (SUV 12.3) with several satellite lesions and hilar nodal metastasis giving her a final stage of T3N2M1. Next generation sequencing: Resected metastatic brain lesion was sent for next generation sequencing which showed presence of EGFR p.L858R and p.H870R mutations and increased EGFR copy number. Other mutations identified included Tp53 p.R175H and CDKN2Ap.H83Y. Tumor was negative for KRAS mutation. EML4-ALK and ROS1 rearrangement were also negative by FISH. References: 1. Pas TD, et al. Activity of Epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations. Journal of Thoracic Oncology. 2011.6(11)1895-1901 2. Tam IY,et al. Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations. Mol Cancer Ther. (2009); 8(8):2142-51 Treatment: Patient received adjuvant gamma knife to the tumor bed of resected brain lesion and in consideration of her oligometastatic disease was started on concurrent thoracic chemo- radiotherapy. She received a total of 60 Gy radiation to the chest with 2 cycles of cisplatin-etoposide. At the completion of chemo-radiotherapy re-staging CT scan chest and abdomen showed no improvement in chest disease with appearance of new metastatic lesion in liver. MRI brain done at that time also showed a new metastatic lesion in parietal calvarial bone for which she received whole brain radiation therapy. At that time she was stared on erlotinib at 150mg/day. Initially patient had poor tolerance to erlotinib with excessive vomiting. Erlotinib dose was reduced to 150mg every other day and once tolerance improved the dose was gradually increased back to 150mg/day. Re- stating CT scan at 2 months showed partial response in primary thoracic tumor as well as almost complete resolution of metastatic lesion in liver. Patient remains on erlotinib at 150mg/day and most recent re-staging CT scan chest /abdomen as well as MRI brain performed 9 months after starting erlotinib show stable disease. Previous reports have showed poor response to EGFR TKI in patients with double EGFR (L858R + p.H870R) mutation (1,2).This case report shows poor response of platinum doublet chemotherapy but good response and prolonged stable disease to EGFR TKI eroltinib in a patient with double EGFR (L858R + p.870R) mutation. Chest CT at start of erlotinib (Sept 2014) Chest CT at 2 months (after starting erlotinib)