Evaluation of the efficiency and toxicity of tyrosine kinase inhibitors in metastatic non small cell lung cancer patients

Methods: In this study, patients with NSCLC who were followed up by the Medical Oncology Unit of Dicle University Faculty of Medicine between 30 May 2013 and 31 December 2022, who received TKI treatments and who continued their follow-up regularly in our center, were retrospectively analyzed. Demographic data of patients, smoking history, pathological diagnosis and mutation results, performance status at diagnosis, clinical stage at diagnosis, treatments received after diagnosis, laboratory and radiological findings in follow-up, side effects and toxicities developed after treatment, levels of toxicities, treatment and progression status, progression-free survival, last control date, final status, and overall survival were analyzed according to the information in the hospital records. Results: The mean age of the patients were 58,10 ± 14,61 years. 40,3% of the patients were male and 59,7% were female. The rates of smoking and non-smoking of the patients were 35,5% and 59,7%, respectively. It was determined that 88,2% of the smoking patients had EGFR, 8,8% ALK and 2,9% BRAF mutations. EGFR mutation was found in 68,4%, ALK in 21,1%, ROS-1 in 5,3% and BRAF mutation in 5,3% of non-smokers. There was no statistically significant difference between the driver mutation rates according to the smoking habits of the patients (p>0,05). 67,7% of the patients started to receive TKI treatment in first line, 27,4% in second line and 4,8% in third line. It was determined that the frequency of fatigue, nausea, vomiting, diarrhea, anemia, acne, liver toxicity was higher in patients receiving anti EGFR treatment compared to other side effects. The frequency of fatigue, nausea, vomiting, thyroid toxicity, proteinuria, anemia was higher in patients taking anti ALK - ROS1 group drugs compared to other side effects. Grade 1 anemia was detected in only 1 of 2 patients who received anti BRAF group drugs. The mean follow-up period of the group receiving anti EGFR in the first line of treatment was 13 months, and the median progression-free survival time of this group was 11,2 (95% CI: 8,50 – 13,90) months. The mean follow-up period of the group receiving anti ALK – ROS 1 in the first line of treatment was 11 months, and the median progression-free survival of this group was 16,0 (95% CI: 6,54 – 25,46) months. The mean follow-up period of the patients who received dabrafenib and trametinib treatment in the first-line therapy was 12 months, and the median progression-free survival time was 11,2 months. The median overall survival time of the anti EGFR group was 17,8 months (95% CI: 12,84 – 22,76) in those administered at one step and 29,6 months (95% CI: 16,72 – 42,48) in those administered in two steps. As a result of Kaplan Meier survival analysis, a significant difference was found between these two groups in terms of survival curves (Log Rank Mantel Cox=4,261; p=0,039). It was determined that the overall survival rate of the patients who received two-step anti EGFR was higher than those who received one-step anti EGFR. The mean follow-up period of all patients was 18 months and the median overall survival was 18,7 (95% CI: 15,14 – 22,26) months. Conclusion: In our study, the PFS and OS values of TKIs were found to be in agreement with the literature. Common side effects in our study were fatigue, diarrhea and anemia. Few patients needed dose reduction and no toxic death was observed. These data are important in terms of showing that TKIs are a more tolerable and suitable option for patients with fewer side effects while increasing survival.