Efficacy and safety study of osimertinib in advanced non-small cell lung cancer (NSCLC) with EGFR mutation.

Abstract

e21150 Background: The frequency of transmission on EGFR is more frequent in women and non-smokers. It is characteristic of the Asian population (10% in the Caucasian race). EGFR tyrosine kinase domain inhibitors (EGFR-TKIs) are the standard first-line therapy in non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of osimertinib (third generation TKI-EGFR) were evaluated in the FLAURA phase III clinical trial, comparing it against first and second generation TKI-EGFR (erlotinib and gefitinib) in patients with advanced NSCLC. The objective is to evaluate the efficacy and safety of osimertinib in routine clinical practice at the Juan Ramon Jimenez Hospital. Methods: Descriptive observational, and retrospective study of patients with advanced NSCLC and EGFR + treated TKI-EGFR in the period 2015-2022. We analyzed (IBM SPSS Statistics 22) sociodemographic and clinical variables, toxicity profile, objective response rate (ORR), treatment response and progression-free survival (PFS) with Kappan-Meier curves. Results: We included 41 patients (p). 24 women (58.5%). The median age 66 years. 61% had a smoking habit (39% active smokers and 22% ex-smokers). 1p South American race, rest Caucasians. Present histologies: adenocarcinoma (87.8%), squamous cell (4.9%) and signet ring cells (2.4%). EGFR mutations: 53.7% exon 19 deletion and 36.6% exon 20 mutation and 9.8% were not specified. In 10 p the T790 mutation was analyzed, positive in 14.6%. Stage at diagnosis: IV (87.8%); III (12.2%). Symptoms at diagnosis: persistent cough (22%), pain (22%), dyspnea (19.5%) and constitutional syndrome (12.2%). Status Performance: 0-1 (85.4%). Pulmonary (48.8%), bone (36.6%), lymph node (29.3%), liver (22%), brain (22%), and adrenal (14.6%) metastases. 58.5% received osimertinib in the first line, 17.1% in the second. ORR: 77.4% partial response, 9.7% complete response and 12.9% disease progression. Toxicity (T) 90.9%. Digestive T: Diarrhea: grade G1 36.7%, G2 13.3%, G3 6.7%; nausea: G1 3.3%; hyporexia: G1 25.8%; hypertransaminasaemia: G1 3.2%. Dermal T: skin dryness: G1 20.7%, G2 10.3%, G3 3.4%; onycholysis: G1 19.4%. Asthenia: G1 25.8%, G2 12.9%, G3 12.9%. Pneumonitis: G1 3.2%, G2 3.2%, G3 6.5%. Hematological T: anemia: G1 6.5%, G2 16.1%, G3 3.2%. Dose reduction to 40 mg (37.5%). 12.5% discontinued osimertinib. mPFS in 1st line (L): 14 m (m). mPFS in 2nd L: 8 m. 95% CI (0-31.5). 95% CI (9.8- 18.1. mOS: 21 m (95% CI: 17.73-24.26). Conclusions: Osimertinib presents an adequate safety profile for patients with G1, G2 toxicities, generally easy to manage in clinical practice. A very low percentage of patients had to discontinue treatment. No fatal adverse event was reported. Our results in OS and PFS, although favorable, are somewhat lower than those of the FLAURA clinical trial, possibly due to dealing with real-life patients and/or the size of the sample, which is not entirely sufficiently representative.