Clinical and Genomic Characteristics of Patients With Advanced NSCLC Who Have Long-Term Response to First-Line Immunotherapy: A Real-World Study

Introduction There is a paucity of data about patients with advanced NSCLC (aNSCLC) with disease control for at least 2 years since the start of first-line (1L) immunotherapy. Methods Databases of five Israeli cancer centers were searched for cases of patients with aNSCLC who commenced 1L treatment with immunotherapy between 2018 and 2021 and had no progression of disease for at least 2 years since treatment initiation. Clinical, pathologic, and genomic sequencing data were retrospectively collected. The end of 2 years from the initiation of treatment was the index date. Progression-free survival (after 2 y) and overall survival (after 2 y) were calculated by Kaplan–Meier method from the index date. Collected variables were examined for correlation with the outcome. Results A total of 206 patients were included, with a median age of 65 years; 64.1% were males and 6.3% were never-smokers. Brain and liver metastases were found in 22.3% and 4.9%, oligometastatic disease in 80.6%; 62.1% had PDL1 greater than or equal to 50%. Mutations in STK11 , KEAP1 and both were found in 3.9%, 0.5% and 0%. At a median follow-up of 25.0 months from the index date, the median Progression-free survival and overall survival after 2 years were not reached (NR) (95% confidence interval: NR–NR). There were 58 patients (28.2%) who progressed after the index date; 24 were rechallenged with immunotherapy. Response to rechallenge was 50%. In multivariate analysis, older age, squamous histologic diagnosis, and liver metastasis were associated with increased risk of death. Conclusions In real-life settings, aNSCLC (at 2 years or longer) who are responders to 1L immunotherapy have high rates of oligometastatic disease, high PDL1, low rates of never-smoking history, baseline liver metastasis, and STK11 or KEAP1 mutations. Except for age, histologic diagnosis, and liver metastasis, long-term survival is not correlated with baseline variables. Approximately a quarter of progress after 2 years of disease control.