Real-World Study Supports Chemotherapy-Free Immunotherapy Combination in Advanced NSCLC
Posted: Thursday, March 19, 2026
Many patients with advanced non–small cell lung cancer (NSCLC) are unable or unwilling to tolerate platinum-based chemotherapy, prompting interest in alternative regimens that maintain efficacy while reducing toxicity. In a recent study published in the Chinese Journal of Cancer Research, Haiyang Chen, MD, and colleagues evaluated a chemotherapy-free treatment strategy for patients with advanced NSCLC. Specifically, the authors examined the real-world effectiveness and safety of combining the antiangiogenic agent anlotinib with PD-1/PD-L1 immune checkpoint inhibitors (ICIs).
Study Details
This prospective, multicenter, real-world study enrolled patients with stage IIIB to IV NSCLC across 28 centers in China between August 2021 and August 2024. Eligible patients were adults with measurable disease who received anlotinib plus an ICI as first- or second-line therapy. Of 320 screened patients, 242 who completed at least two treatment cycles were included in the full analysis set. Treatment consisted of oral anlotinib administered on days 1 to 14 of a 3-week cycle, alongside intravenous PD-1/PD-L1 inhibitors given on day 1. The primary endpoint was progression-free survival. Tumor response was assessed using RECIST 1.1 criteria, with imaging reviewed independently.
Key Results
In the overall cohort, median progression-free survival was 7.8 months (95% confidence interval [CI] = 7.0–9.5 months), and median overall survival was 17.0 months (95% CI = 15.1–19.4 months). Outcomes were more favorable in the first-line setting, where median progression-free survival reached 9.8 months, compared with 6.9 months in the second-line setting. Subgroup analyses suggested that earlier use of the regimen may confer greater benefit, and higher PD-L1 expression was associated with improved outcomes.
Safety findings were consistent with known profiles of ICIs and antiangiogenic therapy. Treatment-related adverse events occurred in 81.8% of patients, though most were grade 1 to 2. Common adverse events included fatigue (56.2%), hypertension (36.4%), and hypothyroidism (32.6%). Grade 3 to 4 adverse events were relatively infrequent (9.1%), with hypertension and fatigue among the most common. Overall, the regimen was considered manageable, particularly compared with the toxicity burden associated with chemotherapy-based combinations.
This study provides real-world evidence supporting a chemotherapy-free approach in a heterogeneous patient population, including those often underrepresented in clinical trials. The findings align with prior clinical trial data suggesting synergy between antiangiogenic agents and immunotherapy, while also highlighting the practical applicability of this approach in routine care. As noted by the study authors, “this multicenter, real-world study demonstrates that the anlotinib-ICI combination regimen exhibits clinically meaningful efficacy and tolerability as a chemotherapy-free alternative for advanced NSCLC.”
DISCLOSURE: For full disclosures of all study authors, visit cjcrcn.org.
