P34.10 Transformation to Small Cell Lung Cancer from an Adenocarcionma EGFR+ as Resistance Mechanism. Utility of Liquid Biopsy in Treatment Selection

Abstract

Tyrosine kinase inhibitors (TKIs) have been shown to be effective in advanced lung cancer with mutation of the EGFR gene. Several mechanisms of resistance to TKIs have been identified, such as: point mutation of the EGFR T790M within exon 205.6, amplification of the MET and Her2 gene, secondary mutations in BRAF-12 and very rarely the histological transformation to small cell lung cancer (SCLC). Case Report CLINICAL CASE : 51-year-old, former tobacco user, diagnosed in 2013 with left locally advanced lung adenocarcinoma, Stage IIIB, EGFR mutated (L858R) by liquid biopsy (LB) because the lake of histological material was not enough to study EGFR in tumoral tissue. Initially received gefitinib 250 mg/day. After 4 years she progressed in 2017, with increase of lung tumor mass with bone compromise. The histological diagnose of lesion showed: Poorly differentiated lung carcinoma with features of SCLC confirmed by Immunohistochemistry, a 2nd LB was performed and informed EGFR L858R mutation in circulating DNA (cDNA). The therapeutic plan was Radiation therapy in rib cage and 6 cycles of chemotherapy platin based plus etoposide, after complete treatment response assessment (RA) showed stable disease. In March 2019 a 3rd LB was performed, an EGFR L858R + in cDNA was still present; so patient restart Gefitinib. A 6-month tomography control informed stable lung images with new liver metastases and a brain CT scan performed because neurological symptoms showed a right frontal cortical lesion of 16 mm x 19 mm. She received whole brain radiotherapy. She archived complete response in CNS by images and significant clinical improvement, but progression, with multiples nodule in the lung and liver . The new liver biopsy demonstrated an infiltration of SCLC, and a 4th LB showed EGFR + L858R mutation. Based in this information it was decided to continue with gefitinib and start a second line chemotherapy, with taxanes, in a concurrent way. At the moment of this report, the patient is still alive with stable disease, after three cycles of chemotherapy, whitout any severe adverse effects, except mild diarrhea and dermatitis. LB has demonstrated in this patient the coexistence of L858 Mutation in blood and SCLC in tumor tissue. The transformation to SCLC in histological tissue biopsy is a very rare mechanism of resistance to TKIs, about 3 % of the cases of the patients with EGFR mutations. LB allows us to select the best treatment for this patient and could detect the absence of other mechanism of resistance, like mutation of the EGFR T790M. At the moment of the presentation of this abstract, there are very few cases and reports about the right treatment of the patient with this uncommon condition in the literature. One of this reports describe a patient with the T 790 M in LB and a transformation to SCLC in tumor tissue, treated with osimertinib plus chemotherapy. A larger number of patients could provide a strong evidence on this issue.