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Abstract
Background Immunotherapy with PD-(L)1-based strategies has rapidly transformed the treatment landscape for non-driver mutation metastatic non-small cell lung cancer (NSCLC). However, it is unclear how recent immunotherapy approvals have translated into real world practice patterns and patient outcomes. This study examined treatment patterns and attrition rates by line of therapy (LOT) among real-world patients with non-driver mutation metastatic NSCLC in the era of immunotherapy.
Methods In this retrospective analysis, adult patients with metastatic NSCLC (2015–2022) and at least one LOT were identified from COTA’s US multi-center NSCLC database of curated longitudinal electronic health records. Patients receiving tyrosine kinase inhibitors or with confirmed EGFR/ALK abnormalities were excluded.
Results Among the 2,107 patients identified, the median age at diagnosis was 69 years, with 45.9% female (table 1) and median follow-up time of 11.9 months. PD-(L)1-based therapy was the most common frontline therapy (55.7%), of which 60.5% was PD-(L)1/platinum combo (figure 1). The use of frontline platinum chemotherapy (without PD-(L)1) decreased from 76.8% in 2015 to <15% after 2019 (table 2). A significant proportion of patients died during each LOT (37.4–42.2% across LOT1–4). Mortality rate during frontline was 37.9% among PD-(L)1/platinum combo users and 45.5% among PD-(L)1 monotherapy users. Less than one third of frontline PD-(L)1 users received subsequent treatment during the observed follow-up. The most common second- and third-line treatment post-frontline PD-(L)1/platinum combo was non-platinum chemotherapy (44.1% and 54.2%). The most common second- and third-line treatment post-frontline PD-(L)1 monotherapy was platinum chemotherapy (25.4%) and non-platinum chemotherapy (55.6%), respectively. Of the 118 frontline PD-(L)1 monotherapy patients with subsequent treatment, 55.9% did not receive platinum-containing regimen as second-line. The overall median LOT duration (treatment duration plus treatment-free interval) and treatment duration for frontline was 5.4 and 2.9 months, respectively, with the longest median duration observed for PD-(L)1/platinum combo (table 3). Frontline PD-(L)1 monotherapy users appear to have longer duration on subsequent lines compared to frontline PD-(L)1/platinum combo users. Overall, a decreasing trend in duration of LOT and treatment was observed as patients advanced to later lines.
Conclusions Even with the incorporation of PD-(L)1-based approaches in the management of frontline metastatic NSCLC, duration of therapy remains short, and most patients do not receive subsequent treatment, reflecting the challenge in controlling advanced disease. Patients who received subsequent lines had decreasing time on treatment with each progressive LOT. These observations underscore the unmet medical need to develop innovative treatment strategies in both frontline and advanced treatment settings.
Ethics Approval COTA’s de-identified real-world database is approved by WCG IRB for use in research (Study #1174746).
Baseline characteristics by frontline treatment in patients with metastatic non-small cell lung cancer
Utilization rate of frontline treatment by year of diagnosis (2015–2022)
Attrition rate by line of therapy in patients with metastatic non-small cell lung cancer
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