Survival outcomes of patients diagnosed with lung adenocarcinoma with ALK gene rearrangement

Introduction: Only 5% of lung adenocarcinomas have the anaplastic lymphoma kinase (ALK) gene rearranged. It gives patients the opportunity to be treated with targeted ALK tyrosine kinase inhibitors (ALK TKI). Methods: We analyzed data of the patients diagnosed with advanced stage ALK positive lung adenocarcinoma in University hospital center Zagreb, Department for pulmonary diseases from January 2018 until December 2020. Results: During this period 64 patients were treated with ALK TKIs, 29 with crizotinib and 35 with alectinib. Out of 29 patients that were treated with crizotinib in the first line, 27 progressed at the time of data cut off and 25 received alectinib in the second line, while one patient was treated with brigatinib. In the third line setting 10 patients were treated with brigatinib or lorlatinib. There were 35 (55%) females with median age 65 years (36-82). Almost half of them (43%) had smoking history with median pack/years 26.9 (2-75). We observed median overall survival (mOS) of 47 months (95%CI 21.6-72.3), while mOS for patients treated with alectinib in the first line was not reached. Median progression-free survival (mPFS) was 12 months (95%CI 6,2 -14,7), but for crizotinib was 8 months (95% CI 5,1 – 10,8) and for alectinib it was not reached. mPFS2 for alectinib is 12 months (95%CI 2,3 – 21,6). Conclusion: We present real-life data on outcomes associated with sequencing of different ALK TKIs. Our data suggest that treatment with alectinib in the first line gives better survival benefit compared to first generation TKIs. To date, no evidence was found directly comparing different ALK inhibitor sequences so real life data are very important in future treatment strategies.