Sintilimab plus anlotinib in later-line treatment of advanced KRAS-mutant NSCLC: a multicenter, retrospective case series

Background Patients with advanced KRAS -mutant non-small cell lung cancer (NSCLC) face a paucity of effective later-line therapies. While combining PD-1 inhibitors with anti-angiogenic agents is a promising strategy, real-world evidence for chemo-free combinations in this specific population remains scarce. Methods This multicenter, retrospective case series evaluated 27 patients with advanced KRAS -mutant NSCLC who received sintilimab (200 mg IV, q3w) plus anlotinib (8–12 mg PO, d1–14, q3w) after ≥1 prior line of therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and safety. Results With a median follow-up of 30.3 months, the median PFS was 7.96 months (95% CI: 5.6–10.3) and median OS was 12.4 months (95% CI: 8.2–16.6). The ORR was 33.3% and the disease control rate was 92.6%. A critical finding was that patients without prior exposure to anti-angiogenic therapy had significantly superior PFS (9.1 vs. 3.0 months, HR = 0.29, p < 0.001) and OS (13.5 vs. 5.7 months, HR = 0.42, p = 0.025). Grade 3–4 treatment-related adverse events occurred in 25.9% of patients, primarily hypertension (11.1%) and hand-foot syndrome (7.4%), with no fatal events. Conclusion This real-world case series suggests that sintilimab plus anlotinib offers promising efficacy and manageable toxicity as a later-line, chemotherapy-free regimen for advanced KRAS -mutant NSCLC. The absence of prior anti-angiogenic therapy emerged as a strong positive predictor for survival, underscoring the importance of strategic treatment sequencing in clinical practice.