Real-World Efficacy of Nintedanib Plus Docetaxel After Progression on Immune Checkpoint Inhibitors: Results From the Ongoing, Non-interventional VARGADO Study

Abstract

Aims: To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy.

Materials and methods: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy.

Results: The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%).

Conclusions: Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.

Keywords: Advanced non-small cell lung cancer (nsclc); angio-immunogenic switch; anti-angiogenic therapy; fast-progressing; immune checkpoint inhibitor (ici) resistance; real-world evidence.