No abstract

Background: 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. Method: Not Applicable Results: 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 pretreatment 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. Conclusion: 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.

e21568 Background: Tirosine Kinasa Inhibitors (TKI) are the standard treatment in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutation. However, eventually patients will progress to TKI. The aim of this study is to determinate if neutrophil-lymphocyte ratio (NLR), RDW-CV and platelet-lymphocyte ratio (PLR) are associated with progression free survival (PFS). Methods: This is a retrospective observational study of a single patient cohort. Clinical records of advanced NSCLC patients that received TKI as first line therapy in ALIADA cancer center since January 2015 and December 2019 were evaluated. NLR, RDW-CV and PLR were calculated from blood counts before beginning of TKI. The statistical analysis was performed with SPSS version 20 and MINITAB 14. Results: 182 patients were diagnosed with advanced NSCLC and 30% of them harbor a EGFR mutation. 43 patients were finally included, 55.8% were women and mean age was 58 years. The 65% of patients had exon19 deletion, 25% exon21 L858R substitution, 7% exon20 T790 mutations and 3% exon18 G719X substitution. 44% of patients received erlotinib, 38% afatinib and 18% osimertinib. The 61.5% of patients achieved partial response; they had a mean NLR, PRL and RDW-CV of 2.98 (0.93–7.41), 238.59 (101.63–863.01) and 13.8 (12.6–15.5) respectively. 17.3% achieved complete response, with a mean NLR, PRL and RDW-CV of 2.93 (1.22–4.64), 204.37 (109.21–417.46) and 13.7 (12.8–15.4). Finally, 9.6% maintain stable disease; with a mean NLR, PRL and RDW-CV of 4.25 (3.6-4.91), 200.7 (196.4-205) and 14.35 (14.3-14.4). 74% of patients progressed. The mean PFS was 24.33 months (95% CI 16.05 - 32.6). Patients that developed progressive disease and those who did not, had no significant difference in the mean NLR (3.98 vs 3.68, p = 0.706) and mean RDW-CV (14.12 vs 14.3, p = 0.655). However, patients with clinical benefit during TKI had a mean PLR of 163.68, meanwhile patients with progressive disease had a mean PLR of 276.54 (T of Student, p = 0.03). Conclusions: In patients with advanced EGFR mutated NSCLC, a high level of PLR is associated with a lower PFS. It is necessary to carry out studies with a bigger amount of population to validate the PLR as a predictive biomarker. To our knowledge this is the first study that analyzes these characteristics in Latin American population.

e21522 Background: The standard treatment for patients with advance EGFR mutated NSCLC are Tirosine Kinasa inhibitors (TKI), we face in our clinical practice a different profile of toxicity; there is limited data of Inflammatory markers in this especial population. The aim of our study is to determine whether neutrophil lymphocyte ratio (NLR), lymphocyte platelet ratio(PLR), RDW-CV and body mass index (BMI) are related to the develop of this toxicity. Methods: We retrospectively analyzed data of patients with EGFRm NSCLC at Aliada Clinic between January 2016 to December 2019. Inflammatory markers were obtained from laboratory tests performed during the first visit as outpatient. The BMI kg/m2 at the start of the treatment was defined as the weight (kg) divided by the height (m) squared. Adverse event (AE) were graded according CTCAE v5.0. Results: A total of 164 patients were diagnosed with advanced NSCLC, of these 50 patients were assessed, 29 women and 21 men. The average age was 58.9 years, median of 59.5 ( 38 to 83; SD: 11.7). The most frequent EGFR mutation was deletion 19 (59.6%) followed by L858R mutation ( 23.1%) . The median BMI was 25.18 (16.2 to 41.3 kg/m2) 46.2% were normal, 36.5% were overweight, and 11.5 % were obese. 80% present any grade of AE. The most frequent AE was skin related: 75% (90 % grade I or II) follow by gastrointestinal: 57.6% (74 % grade I or II). There were no significant differences between NLR according to toxicity grade I-II vs III-IV (media: 3.44 and 4.32; P = 0.46); PLR according toxicity grade I-II vs III-IV (media: 229.41 and 251-50; P = 0.78); and RDW-CV according to toxicity grade I-II vs III-IV (media: 14.17 and 14.4; P = 0.74). Similarly, no significant differences were observed among toxicity profiles in relation to BMI (p = 0.2). Finally, there was no impact of severity of toxicity on progression-free survival (p = 0.64) or overall survival 24,33 months (IC 95% 16,05 – 32,6; p = 0.9). Conclusions: There was no relation between inflammatory markers and the grade of toxicity in patients with EGFRm advance NSCLC receiving TKIs. We suggest increase the population to validate our results.

Among these patients, 35 (58.3%) patients were female. And 14 (23.3%) of them had brain metastasis. Till August 2020, 57 of the patients received at least once tumor assessment. 51 of them achieved partial response, 6 of them had stable disease and no patients had disease progression. The ORR was 89.5%, while the DCR was 100 %. The most common grade 3 adverse event (AE) are rash (15.3 %), oral mucositis (10.2%) and diarrhea (8.5 %). A grade 4 hypertension were observed. Conclusion: This is the first study of the new combination of anlotinib plus erlotinib. The results suggest that this strategy could be a new first-line therapy in EGFRmutated NSCLC patients. The long-term outcomes will be revealed in the future.