P49 Lung Adenocarcinoma with Double Heterozygote EGFR mutation and Combined Resistance: ALK Translocation and EGFR T790M

Abstract

About 14% of patients with metastatic lung adenocarcinomas in our population have tumors harboring EGFR mutations or deletions. Herein we report the case of a patient with lung adenocarcinoma with a double deletion of EGFR who had a partial response for 6 months treated with afatinib and, upon progression, an EGFR T790M mutation and an ALK translocation were detected. Not Applicable Case Report: A 32-year-old male, non-smoker, presents with abdominal pain, cough and fatigue. Abdominal ultrasound showed a large left adrenal lesion and the chest X-Rays, a consolidation in the right inferior lobe. PET-CT with 18FDG scan was performed evidencing a 7.2 cm tumor in the right lower lobe with high affinity for FG, as well as mediastinal and retroperitoneal enlarged lymph nodes, right adrenal mass, left acetabular and posterior costal lesion. A diagnostic transbronchial tumor-biopsy showed an undifferentiated carcinoma TTF1 + (T3N3M1c). EGFR status, assessed by PCR and sequencing, showed an exon 19 deletion (delE746_A750) with no ALK (clon D5F3) nor ROS1 (clon D4D6) translocations by immunohistochemistry (IHC). Next generation sequencing (NGS) with the Oncomine TM Focus Assay panel (Ion 520 Chip) revealed a double deletion in EGFR (p.delE746_A750 and p.delL747_T751insQ) in separate reads. The patient started treatment with afatinib and achieved a partial response at 3 months. After 6 months he experienced progressive lung abnormalities (metastasis???) and brain and cerebellar metastasis consistent with disease progression. Afatinib was stopped and both CNS lesions were resected. Standard ALK, ROS1 and EGFR determinations were repeated on brain tissue. An ALK translocation was identified by IHC and confirmed by FISH as well as the EGFR exon 19 deletion p.delE746_A750, without T790M mutation. The pre-treatment lung biopsy was reviewed and was negative for ALK translocation. EGFR testing in circulating tumor DNA was positive for the T790M secondary resistance mutation. Patient had rapid retroperitoneal progression with ascites, bleeding and abdominal pain requiring surgical intervention. Crizotinib was started without response and the patient died. Here we report a case of a patient achieving a partial response with afatinib in a tumor with two EGFR deletions and the co-occurrence of secondary EGFR T790M mutation and ALK translocation as mechanism of resistance. In addition, the lack of detection of the EGFR deletion p.delL747_T751insQ, suggests a complex subclonal evolution secondary to tumor heterogeneity.