The evolving survival landscape in advanced non-small cell lung cancer: an interrupted time series analysis

Treatment of advanced non-small cell lung cancer (NSCLC) has shifted from chemotherapy to targeted therapy and immunotherapy. We aimed to evaluate the effects of these novel therapies on advanced NSCLC in real-world setting. We conducted a retrospective cohort study using the SEER database of patients with advanced NSCLC receiving systemic therapy. Patients were stratified into three periods: chemotherapy (1992–2002), targeted therapy (2003–2014), and immunotherapy (2015–2022). We used interrupted time series analysis to evaluate changes in overall survival rate and cancer-specific survival rate (CSSR). The analysis included 32,899 patients. Compared to chemotherapy (11.9 months), median overall survival was significantly longer with targeted therapy (19.3 months) and immunotherapy (27.4 months). The 3-year CSSR increased by 0.36% and 0.89% per year following targeted therapy and immunotherapy, respectively. Adenocarcinoma showed sustained improvement in 3-year CSSR after targeted therapy (0.52% per year) and immunotherapy (0.83% per year), while squamous cell carcinoma showed no significant change. Most subgroups showed continuous survival improvement after immunotherapy. The introduction of targeted therapy and immunotherapy has produced significant survival improvement in adenocarcinoma, with the most pronounced benefits with immunotherapy. Treatment efficacy varies across subgroups highlighting the need for further investigation to optimize personalized therapy. Why was this study done? Lung cancer remains one of the leading causes of cancer-related death worldwide. Over the past 30 years, treatments for advanced non-small cell lung cancer have changed greatly, moving from chemotherapy to newer treatments such as targeted therapy and immunotherapy. Most evidence for these treatments comes from clinical trials, which often include younger and healthier patients. It is therefore important to understand whether these treatments improve survival for people treated in routine clinical practice. What did the researchers do? The researchers analyzed information from a large United States cancer database that collects data on cancer diagnosis and survival. They studied adults with advanced non-small cell lung cancer diagnosed between 1992 and 2022. Patients were grouped according to the treatment era in which they were diagnosed: chemotherapy, targeted therapy, or immunotherapy. What did the researchers find? Survival gradually improved over the 30-year study period. People diagnosed during the targeted therapy and immunotherapy eras lived longer, on average, than those treated with chemotherapy alone. The largest survival improvements were seen after immunotherapy became available. Survival gains were not the same for all patients. People with lung adenocarcinoma benefited more than those with lung squamous cell carcinoma, and differences were also observed by age, sex, race, and income level. What do the results mean? These findings show that newer lung cancer treatments have improved survival in real-world care, but the benefits are uneven across patient groups.