The purpose of this study is to demonstrate the non-inferiority of treatment pause versus treatment continuation in good or intermediate risk with only one adverse prognostic factor as per IMDC mRCC patients with a confirmed objective response between the end of the 11th month to th end of the 13th month of treatment with PD-1/PD-L1 ICI plus VEGFR-TKI. Tolerance and quality of life of treatment pause with PD-1/PD-L1 ICI + VEGFR-TKI compared to treatment continuation will be reported. In France, its impact on healthcare resource utilization will also be assessed.
Although multiple combinations therapies in particular PD-1/PD-L1 immune-checkpoint inhibitors (PD-1/PD-L1 ICIs) in combination with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are approved and have improved patient's outcomes with mRCC, they are maintained until disease progression and treatment pause after an objective response has not been fully explored \[5-7\]. The good-risk population is characterised by prolonged survival therefore a treatment pause in this population could impact the quality of life, safety and total cost of care, without impacting outcome. As well, intermediate risk population group is heterogeneous, while the one's with only one adverse prognostic factor seems to be closed to the outcome of good risk population \[11-15\]. As the purpose of the study is to target patients with an objective response, there is already a selection of patients with a better outcome. Patient will be randomised after 11 to 13 months of treatment with PD-1/PD-L1 ICI plus VEGFR-TKI (treatment pause versus treatment continuation) and follow every 3 months for a period of 12 months following by 12 additional months for survival follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
The study will enroll patients achieving an objective response beween the end of the 11th month and the end of the 13th month of treatment with the combination PD-1/PD-L1 ICI + VEGFR-TKI as recommended in the Summary of Product Characteristics (SmPC)
Combination regimens discontinuation until progression with the possibility to resume initial combination regimens at progression
CH de la Cote Basque - Service d'Oncologie
Bayonne, France
CHU de Bordeaux - Service d'Oncologie
Bordeaux, France
Centre François Baclesse - Service d'Oncologie
Caen, France
Centre Jean Perrin - Service d'Oncologie
Clermont-Ferrand, France
AP-HP - Henri Mondor - Service d'Oncologie
Créteil, France
Centre Georges-François Leclerc - Service d'Oncologie
Dijon, France
CHU Grenoble Alpes - Service d'Oncologie
Grenoble, France
CHU de Limoges - Service d'Oncologie
Limoges, France
Polyclinique de Limoges - Service d'Oncologie
Limoges, France
Centre Leon Berard - Service d'Oncologie
Lyon, France
...and 16 more locations
Proportion of participants without progression
Disease progression at up to 12 months after randomisation will be based on a blinded independent central review (BICR) according to RECIST v1.1 criteria, with tumor assessment performed every 12 weeks during study participation
Time frame: Up to 12 months after randomisation
Overall safety profile and tolerability event
Proportion of participants who experience an adverse event or serious adverse event and mean number of adverse events or serious adverse events up to 12 months after randomisation
Time frame: Up to 12 months after randomisation
Overall survival (OS)
OS is defined as the time between the date of randomisation and the date of death due to any cause
Time frame: From randomisation until 2 years of follow-up
Progression-free survival (PFS)
PFS is defined as the time between date of randomisation and the first date of the documented disease progression, or death due to any cause, whichever occurs first
Time frame: From randomisation until 2 years of follow-up
Mean change in quality of life
Measured by the NCCN functional assessment of cancer therapy-kidney symptom index (FKSI-19). The NCCN FKSI-19 is a 19-item scale that measures tumor specific health-related quality of life in kidney cancer participants. A higher score indicates fewer symptoms
Time frame: Up to 12 months after randomisation
Quality-adjusted survival
The quality-adjusted time without symptoms or toxicity (Q-TWiST) is a simultaneous assessment of time without toxicity or disease progression, which essentially examines the trade-off between AEs and treatment benefits
Time frame: Up to 12 months after randomisation
Anxiety and depression
Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation
Time frame: Up to 12 months after randomisation
Site and distribution of the sites of progression: known lesions, new lesion(s) or both
Time frame: From randomisation until 2 years of follow-up
Distribution of treatment modality after progression
Proportion of participants treated after progression with surveillance, focal treatment or general treatment
Time frame: From randomisation until 2 years of follow-up
Percentage of patients with status SD or in objective response at 6 months after restarting PD-1/PD-L1 ICI + VEGFR-TKI
Time frame: From randomisation until 2 years of follow-up
Healthcare resource utilisation
Costs of care will be estimated in the perspective of the French Healthcare System over a 12-month times horizon. Conventional tariffs of hospitalizations will be used to calculate costs
Time frame: Up to 12 months after randomisation
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