Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody–drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives.

Real-world data on patients with ROS1-positive advanced non-small cell lung cancer (NSCLC) remain scarce. In this descriptive observational retrospective cohort study, we describe characteristics, treatments, and real-world progression-free survival (rwPFS) and overall survival (OS) among patients with ROS1-positive advanced NSCLC (de novo or recurrent) using secondary data pooled from clinical sites in Canada, France, Germany, Portugal, and Spain as part of the Oncology Evidence Network. Site-specific patient inclusion periods occurred between 2009 and 2023, with follow-up to 2024, allowing ≥1 year of potential follow-up at each site. In total, 108 patients were included, with most (n = 105; 97.2%) having a de novo diagnosis of advanced NSCLC. 103 patients (95.4%) received ≥1 line of systemic anticancer therapy (SACT), of which 65 (63.1%) received first-line targeted therapy, mostly crizotinib monotherapy (n = 45) or crizotinib-based regimens (n = 10), with a median (95% CI) rwPFS and OS of 14.0 (8.3–19.8) and 47.9 (27.3–not estimable) months, respectively. Thirty-eight of the 103 SACT-treated patients (36.9%) received first-line non-targeted therapy, mostly platinum-based chemotherapy (n = 26); median (95% CI) rwPFS and OS were 9.0 (7.5–11.0) and 29.3 (17.7–65.7) months, respectively. Results from this study indicated a tendency for longer survival using currently available ROS1-targeted versus non-targeted therapy for patients with ROS1-positive advanced NSCLC. Nevertheless, survival outcomes were limited, highlighting the importance of more effective emerging treatments for ROS1-positive disease.