Continued EGFR-TKI plus anti-angiogenic therapy versus chemotherapy after EGFR-TKI progression in EGFR-mutated non-small cell lung cancer: a real-world cohort study

The optimal treatment after progression on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR -mutated non-small cell lung cancer (NSCLC) remains unclear. We compared continuing EGFR-TKI therapy combined with anti-angiogenic treatment versus chemotherapy after EGFR-TKI progression. This retrospective cohort study included stage IIIB-IV EGFR -mutated NSCLC patients who progressed on EGFR-TKIs and subsequently received either continued EGFR-TKI plus anti-angiogenic therapy or chemotherapy with or without anti-angiogenic therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events. Propensity score matching (PSM) and multivariable Cox regression analyses were performed to reduce potential confounding. Of 327 patients, 137 received EGFR-TKI plus anti-angiogenic therapy and 190 received chemotherapy. At a median follow-up of 56.7 months, Median OS was 21.8 vs. 15.7 months (HR 0.69, 95% CI 0.53–0.90; P = 0.006), and PFS was 6.6 vs. 4.4 months (HR 0.58, 95% CI 0.46–0.74; P < 0.001); benefits persisted after PSM (OS: 22.6 vs. 13.6 months, HR 0.60, P = 0.003; PFS: 6.2 vs. 4.4 months, HR 0.54, P < 0.001). Clinical benefit was most pronounced in prior EGFR-TKI responders. Although ORR was higher with chemotherapy (27.4% vs. 10.2%; P = 0.001), DCR was similar (76.9% vs. 83.2%; P = 0.161). Grade ≥ 3 treatment-related adverse events were 18% vs. 23% (EGFR-TKI plus anti-angiogenic therapy vs. chemotherapy). After EGFR-TKI progression, continued EGFR-TKI plus anti-angiogenic therapy may improve OS and PFS versus chemotherapy with manageable toxicity, especially in prior responders. It could be a chemotherapy-sparing option for selected responders with caution.