Real-World Efficacy of Docetaxel Plus Nintedanib After Chemo-Immunotherapy Failure in Advanced Pulmonary Adenocarcinoma

Metzenmacher, Martin; Rizzo, Filippo; Kambartel, Kato; Panse, Jens; Schaufler, Diana; Scheffler, Matthias; Azeh, Ivo; Hoiczyk, Mathias; Turki, Amin T.; Atz, Judith; Buchner, Hannes; Hoffmann, Christopher M.; Christoph, Daniel C.

doi:10.2217/fon-2021-0424

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…In this post hoc analysis, 14.9%/85.1% of patients received nintedanib plus docetaxel in the second line/third line or later; median PFS was 4.6 months, median overall survival was 8.8 months and the DCR was 78.2% [7]. Furthermore, the DCR in VARGADO cohort B was also consistent with that reported in other real-world analyses of third-line nintedanib plus docetaxel in advanced lung adenocarcinoma after failure on first-line chemotherapy and second-line ICI therapy (82e83%) [3,21]. A clear biological rationale for the use of anti-angiogenic agents (such as nintedanib) after ICI therapy is provided by the growing appreciation that angiogenesis and antitumour immunity are interlinked processes [8,9,22,23].…”

Section: Discussionsupporting

confidence: 80%

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

Grohé¹,

Blau

Gleiber

et al. 2022

Clinical Oncology

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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 ¼ 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and secondline 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 ¼ 32; one complete response and 31 partial responses) and the disease control rate was 86% (n ¼ 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n ¼ 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.

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Section: Discussionsupporting

confidence: 80%

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

Grohé¹,

Blau

Gleiber

et al. 2022

Clinical Oncology

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“…Specifically, the VARGADO cohort demonstrated a mPFS of 6.4 months, with a 1-year OS rate of 52% in the third-line setting ( 16 ). Furthermore, another German cohort reported a mOS of 8.4 months in adenocarcinoma histology specifically ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…First, this is a single-center, retrospective analysis, and as such these observations should be confirmed in a prospective fashion. The Phase II Lung-Map S1800A study evaluated ramucirumab with pembrolizumab combination therapy compared to standard of care chemotherapy, of which two-thirds of the control arm received ram+doc, and was found to demonstrate an OS benefit ( 17 ). Post-hoc analyses will be required to understand the true PFS and OS estimates seen in this sub-group, however.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and outcomes of ramucirumab and docetaxel in patients with metastatic non-small cell lung cancer after disease progression on immune checkpoint inhibitor therapy: Results of a monocentric, retrospective analysis

Kareff

Gawri²,

Khan³

et al. 2023

Front. Oncol.

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Current first-line standard therapy for metastatic non-small cell lung cancer without driver mutations involves chemotherapy and immunotherapy combination. Prior to the advent of immune checkpoint inhibition, REVEL, a randomized phase III trial demonstrated improved progression-free and overall survival with ramucirumab and docetaxel (ram+doc) in patients who failed platinum-based first-line therapy. Long-term outcomes related to second-line ramucirumab and docetaxel after first-line immunotherapy exposure remain unknown. We analyzed outcomes for 35 patients from our center whom received ramucirumab and docetaxel following disease progression on chemotherapy and immunotherapy combination. Median progression-free survival among patients who received ram+doc after exposure to immunotherapy was 6.6 months (95% CI = 5.5 to 14.9 months; p<0.0001), and median overall survival was 20.9 months (95% CI = 13.4 months to infinity; p<0.0001). These outcomes suggest that there may a synergistic benefit to combining chemotherapy with anti-angiogenic therapy after immunotherapy exposure. Future analyses should be evaluated prospectively and among a larger patient subset.

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“…As LUME-Lung 1 was undertaken prior to the era of first-line ICIs, only limited data are available assessing the activity of nintedanib plus docetaxel following immunochemotherapy. Moreover, almost all studies undertaken to date have assessed nintedanib plus docetaxel in a third-line setting after successive chemotherapy and ICI monotherapy; in these studies, nintedanib plus docetaxel was associated with an unprecedentedly high response rate in this setting (36.5-58.3%), and encouraging PFS (3.2-6.4 months) (17)(18)(19)(20)(21). While these studies have demonstrated clinical activity of the combination, its activity following first-line immunochemotherapy is uncertain.…”

Section: Introductionmentioning

confidence: 99%

Nintedanib plus docetaxel after progression on first-line immunochemotherapy in patients with lung adenocarcinoma: Cohort C of the non-interventional study, VARGADO

Grohé¹,

Wehler²,

Dechow³

et al. 2022

Transl Lung Cancer Res

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Background: Immune checkpoint inhibitors (ICIs) with or without chemotherapy represent first-line standard of care for patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. The most appropriate second-line therapy after failing immunochemotherapy remains an open question. Nintedanib, an oral triple angiokinase inhibitor that targets the vascular endothelial growth factor receptor, fibroblast growth factor receptor, and, platelet-derived growth factor receptor, in combination with docetaxel, is approved for treatment of advanced NSCLC (adenocarcinoma histology) following progression on first-line chemotherapy. Methods: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional study investigating the efficacy and safety of nintedanib plus docetaxel following first-line chemotherapy with or without ICIs in patients with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma histology. This analysis focuses on Cohort C, which enrolled patients who had received prior first line chemotherapy with ICIs. Patients received second-line docetaxel (75 mg/m 2 ) by intravenous infusion on Day 1, plus oral nintedanib (200 mg twice daily) on Days 2-21 of each 21-day cycle during routine clinical care. The primary endpoint is overall survival (OS) rate 1 year after the start of treatment with nintedanib plus docetaxel.Secondary endpoints include progression-free survival (PFS), OS, and disease control rate (DCR). Safety was also assessed.Results: Among 137 patients treated, the median age was 63 years (range: 37-84); 57 patients (41.6%) were female, most patients had Eastern Cooperative Oncology Group performance status of 0 (28.5%) or 1 (43.1%); 118 (86.1%) had stage IV NSCLC and 27 (19.7%) had brain metastases. Most (n=120, 87.6%) patients had received pembrolizumab/pemetrexed/platinum-based chemotherapy as first-line treatment.In 80 patients with available response data, the DCR was 72.5% (complete response: 1.3%; partial response: 36.3%; stable disease: 35.0%). Median progression-free survival was 4.8 months (95% confidence interval: 3.7-6.6). OS data were immature. Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were reported in 62 (45.3%), 50 (36.5%), and 40 patients (29.2%), respectively.Conclusions: This analysis indicates that nintedanib plus docetaxel represents an effective second-line treatment option in patients with advanced adenocarcinoma NSCLC following progression on first-line immunochemotherapy. The safety profile was manageable with no unexpected signals.

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Real-World Efficacy of Docetaxel Plus Nintedanib After Chemo-Immunotherapy Failure in Advanced Pulmonary Adenocarcinoma

Cited by 8 publications

References 26 publications

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

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

Efficacy and outcomes of ramucirumab and docetaxel in patients with metastatic non-small cell lung cancer after disease progression on immune checkpoint inhibitor therapy: Results of a monocentric, retrospective analysis

Nintedanib plus docetaxel after progression on first-line immunochemotherapy in patients with lung adenocarcinoma: Cohort C of the non-interventional study, VARGADO

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