Anaplastic lymphoma kinase (ALK) and ROS 1– positive advanced NSCLC: A real-world institutional experience.

Abstract

e21074 Background: A novel fusion gene of EML4-ALK and ROS 1 has been identified in a subset of non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 and ROS1 fusion gene demonstrate unique clinicopathological characteristics and treatment with targeted therapy led to improved survivals. Various clinical trials had shown the efficacy of ALK inhibitors, and they had become the standard of care. The real-world data of ALK inhibitors from a developing country like India is sparse and the present study was designed to analyze the incidence and outcomes of ALK positive NSCLC. Methods: Data of advanced NSCLC patients diagnosed between 2016 and 2022 with ALK and ROS1 positivity was analyzed. Detection of ALK was done by IHC or fluorescent in situ hybridization (FISH) and ROS1 was done by FISH. Results: A total of 776 advanced NSCLC patients between 2016 and 2022 were tested for ALK of which 63(8.1%) were positive. The median age at presentation was 50 years (range, 19-80 years). Of 63 patients, 34(54%) and 29(46%) were males and females. Cough (83%) was the most common symptom at presentation followed by breathlessness (73%), anorexia (59%) weight loss (59%) and chest pain (43%). The median duration of symptoms was 3 months (range, 1-18). 44(86%) patients were never smokers and 9(14%) patients had history of smoking or tobacco usage. The most common site of metastases was opposite lung (59%) followed by bone (50%), pleural effusion (41%) and brain metastasis were seen in 13(21%) patients. Adenocarcinoma was the most common histology (95%). Detection of ALK positivity was done by IHC and FISH in 45(72%) and 18(28%) patients. Of 63 patients, 52 patients received at least 4 months of treatment and were assessed for survival. First line therapy was crizotinib, chemotherapy followed by maintenance crizotinib, ceritinib, Alectinib in 40(77%), 4(7.7%), 6(11.5%) and 2(3.8%) patients respectively. At a median follow up of 14 months, the one-year progression free and overall survival was 71% and 75% respectively. The 2 year and 3-year OS were 54% and 30% respectively. Of 322 patients tested for ROS1, 9(2.8%) were positive for ROS1 translocation and received first line therapy with crizotinib. The one-year PFS and OS of ROS 1 positive patients were 75% and 89% respectively. Conclusions: ALK and ROS1 positivity was seen in 8.1% and 2.8% of advanced NSCLC patients. Majority of patients were never smokers. Opposite lung and bone were the most common site of metastases. Approximately more than half of the patients had two-year survival rate and survivals are almost similar to clinical trials. Crizotinib is well tolerated in majority of patients.