Trial to Evaluate Safety and Efficacy of Vinorelbine With Metronomic Administration in Combination With Atezolizumab as Second-line Treatment for Patients With Stage IV Non-small Cell Lung Cancer

Summary

The majority of patients diagnosed with advanced NSCLC are treated with platinum-doublet chemotherapy regimens, except those harboring specific oncogenic drivers such as epidermal growth-factor-receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In the second-line setting, response rates remain low and median survival rarely exceeds 10 months. Over the past few years, several checkpoint inhibitors targeting programmed cell death protein-1 (PD1) or its ligand (PDL1) used as second-line therapies generated evidence of improving survival and, more recently, as first-line NSCLC treatment. Although pembrolizumab (anti-PD1) was recently approved as first-line treatment for patients with at least 50% of their NSCLC cells expressing PDL1, many patients are still not benefiting from this first-line agent. For patients with relapsed NSCLC, atezolizumab (anti-PDL1) prolonged survival compared to docetaxel in the phase II POPLAR and phase III OAK trials. Novel concepts of synergic action between immunotherapy and chemotherapy have emerged recently. However, those types of treatments are given for different durations: chemotherapy is allowed for only a short period (rarely exceeding 6 cycles), while anti-PDL1 can be continued for several months until loss of its clinical benefit. Metronomic chemotherapy is defined as low-dose and frequent chemotherapy administration, without prolonged drug-free breaks. Metronomic administration of oral vinorelbine has been tested against breast cancer and advanced refractory NSCLC. The combination could have immunostimulatory effects: induction of immunogenic cancer-cell death, enhancement of antigen presentation through dendritic cell modulation, increased cancer-cell immunogenicity, preferential depletion of regulatory T cells, modulation of myeloid-derived suppressor cells, enhancement of the cytotoxic activity of immune-effector cells.

Timeline

Start

2019-01-24

Primary completion

2021-01-04

Completion

2022-02-23

Outcome

Missed primary endpoint

paper did not achieve the predefined PFS threshold. PMID 36868180 ↗

Publications

• Results Vergnenegre A, Monnet I, Ricordel C, Bizieux A, Curcio H, Bernardi M, Corre R, Guisier F, Hominal S, Le Garff G, Bylicki O, Locher C, Geier M, Chouaid C, Robinet G; GFPC team. Safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination in stage IV non-small-cell lung cancer: An open-label phase II trial (VinMetAtezo). Lung Cancer. 2023 Apr;178:191-197. doi: 10.1016/j.lungcan.2023.02.020. Epub 2023 Feb 27.
• Vergnenegre A, Monnet I, Bizieux A, Bernardi M, Chiapa AM, Lena H, Chouaid C, Robinet G. Open-label Phase II trial to evaluate safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination for stage-IV non-small-cell lung cancer - VinMetAtezo trial, (GFPCdouble dagger 04-2017). Future Oncol. 2020 Feb;16(4):5-10. doi: 10.2217/fon-2019-0730. Epub 2020 Jan 2.

Drugs

Indications