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

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

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.

Informations de copyright

2022 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-1018/coif). CG reports consulting fees from Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim; payment for expert testimony from Boehringer Ingelheim; support for attending meetings and/or travel from Boehringer Ingelheim; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for DKG DGP. TW reports grants or contracts from Boehringer Ingelheim in support of an investigator-initiated trial (NCT04413201); consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Serono, Merck Sharp & Dohme, Pfizer, Roche/Genentech; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genentech; payment for expert testimony from Takeda, Roche; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, Celgene, Pfizer, Roche/Genentech; participation on a data safety monitoring or advisory board from Boehringer Ingelheim, Roche, AstraZeneca; research funding from AstraZeneca, Boehringer Ingelheim, Roche/Genentech. S Henschke reports provision of study data as part of the VARGADO study and review of the manuscript (no payment); grants or contracts from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Merck Sharp & Dohme, Roche; consulting fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Merck Sharp & Dohme, Roche; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Merck Sharp & Dohme, Roche; support for attending meetings and/or travel from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Merck Sharp & Dohme, Roche; participating on an advisory board for Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Merck Sharp & Dohme, Roche; equipment, materials, drugs, medical writing, gifts or other services from Boehringer Ingelheim in the context of participation in the VARGADO study. WS reports consulting fees from Boehringer Ingelheim (served in an advisory board and fees paid to the author); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim (paid to the author). ID reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim Pharma GmbH, Bristol-Myers Squibb GmbH & Co KgaA, Takeda Pharma GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, AstraZeneca Pharma GmbH, Merck Sharp & Dohme GmbH; payment for expert testimony, support for attending meetings and/or travel, and participation on a data safety monitoring board or advisory board from Siehe Punkt 5. S Hammerschmidt reports consulting fees from Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim. HMH reports research funding from Roche, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca; honoraria from Roche, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, Merck Sharp & Dohme, Merck, Eisai, Janssen; consulting fees from Roche, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, Merck Sharp & Dohme, Merck, Eisai, Janssen; travel support from AstraZeneca, Janssen. CS reports recruitment of patients and manuscript review and approval as support for the present manuscript; honoraria or presentations from AstraZeneca and Bristol-Myers Squibb to institution and to self. S Krüger reports support for the present manuscript from Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim. JA reports employment with Boehringer Ingelheim. R Kaiser reports employment with Boehringer Ingelheim and patent (EP 2994125). TD has no conflicts of interest to declare.