Impact of First Line Antiangiogenic Therapy Duration on Nivolumab Outcome in Metastatic Renal Cell Carcinoma Patients Treated in the GETUG-AFU 26 NIVOREN.
Advanced Renal Cell Carcinoma
Immune Checkpoint Inhibitor
Response
Survival analyses
Tyrosine Kinase Inhibitor
Journal
Clinical genitourinary cancer
ISSN: 1938-0682
Titre abrégé: Clin Genitourin Cancer
Pays: United States
ID NLM: 101260955
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
10
03
2023
revised:
12
07
2023
accepted:
16
07
2023
medline:
27
11
2023
pubmed:
28
8
2023
entrez:
27
8
2023
Statut:
ppublish
Résumé
In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC. Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included. Response rate, clinical benefit, progression free survival (PFS) and overall survival (OS) were prospectively analyzed depending on the duration of the first line (< 6 months, ≥6 months) and exploratory in patients with long first line exposure (≥18 months). The circulating levels of 8 plasma proteins and cytokines at baseline were collected and compared according to first line antiangiogenic duration. Among 354 patients, 127 (36%) and 227 (64%) patients had received first line antiangiogenic for < 6months and ≥ 6months respectively. Respective duration of first line therapy was not associated with objective response to nivolumab (20.5% vs. 23.9%, P = .50), or PFS (HR 0.92; P = .421). Median OS was respectively 16.6 and 31.3 months in the <6 and ≥6 months subgroups respectively. Adjusted on international metastatic renal cell carcinoma database consortium risk, age and metastatic site, OS was longer in patients with longer treatment duration in the first line setting (HR 0.73; P = .017). Duration of first line VEGFR TKI was independent from circulating levels of 8 proteins and cytokines at nivolumab baseline. Nivolumab activity in second line is independent from first-line duration of VEGFR TKI. However, first line VEGFR TKI duration ≥ 6 months is associated with longer OS.
Sections du résumé
BACKGROUND
BACKGROUND
In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC.
METHODS
METHODS
Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included. Response rate, clinical benefit, progression free survival (PFS) and overall survival (OS) were prospectively analyzed depending on the duration of the first line (< 6 months, ≥6 months) and exploratory in patients with long first line exposure (≥18 months). The circulating levels of 8 plasma proteins and cytokines at baseline were collected and compared according to first line antiangiogenic duration.
RESULTS
RESULTS
Among 354 patients, 127 (36%) and 227 (64%) patients had received first line antiangiogenic for < 6months and ≥ 6months respectively. Respective duration of first line therapy was not associated with objective response to nivolumab (20.5% vs. 23.9%, P = .50), or PFS (HR 0.92; P = .421). Median OS was respectively 16.6 and 31.3 months in the <6 and ≥6 months subgroups respectively. Adjusted on international metastatic renal cell carcinoma database consortium risk, age and metastatic site, OS was longer in patients with longer treatment duration in the first line setting (HR 0.73; P = .017). Duration of first line VEGFR TKI was independent from circulating levels of 8 proteins and cytokines at nivolumab baseline.
CONCLUSION
CONCLUSIONS
Nivolumab activity in second line is independent from first-line duration of VEGFR TKI. However, first line VEGFR TKI duration ≥ 6 months is associated with longer OS.
Identifiants
pubmed: 37635052
pii: S1558-7673(23)00174-X
doi: 10.1016/j.clgc.2023.07.008
pii:
doi:
Substances chimiques
Nivolumab
31YO63LBSN
Vascular Endothelial Growth Factor A
0
Protein Kinase Inhibitors
0
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
643-652Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Disclosure GGD, CD, BE : no conflict of interest; SN:Honoraria: Bristol-MyersSquibb; Ipsen; MSD Oncology; Novartis; Pfizer.Consulting or advisory role e Bristol-Myers Squibb;Ipsen; MSD Oncology; Novartis; Pfizer. ResearchFunding: IPSEN (Inst); Pfizer (Inst). Travel, accommodations, and expenses :Bristol-Myers Squibb;IPSEN; Novartis; Pfizer. . GG: Speaker bureau: Janssen, Amgen, BMS, IPSEN, AAA, Astra Zeneca, Bayer, Pfizer Merck, Astellas. Recipient: my institution.Board: Janssen, Amgen, BMS, Curium, Bayer, Pfizer Merck. Recipient: my institution.Expert: BMS, Bayer, Pfizer/ merck. Recipient: my institution. BL: personal fees from Pfizer, Ipsen, MSD, Eisai, Astellas Pharma, and Janssen andnonfinancial support from Pfizer, Bristol Myers Squibb, and MSD; CC: advisory board ordata safety monitoring committee for Ipsen, Pfizer, Esaï, and GSK;and has received support for travel or meetings from Pfizer. SO : fundings: Astellas, Astra Zeneca, Ipsen, Janssen, MSD, Pfizer, Roche, Sanofi, Bayer, BMS and Novartis. PB: Honoraria Astellas Pharma; BMS; IPSEN;Janssen-Cilag; Merck KGaA; MSD; Novartis; Pfizer.Consulting or advisory role e Amgen; AstraZeneca;BMS; Eisai; Ipsen; Janssen-Cilag; Merck KGaA; MSDOncology; Pfizer. Travel, accommodations, and expenses :Astellas Pharma; BMS; IPSEN; Janssen-Cilag;MSD; SL:Honoraria: BMS; Ipsen; Merck serono;Pfizer. Consulting or advisory role: Ipsen; DB:consulting and advisoryfees from Astellas Pharma, AstraZeneca, Bristol-MyersSquibb, Ipsen, Janssen-Cilag, MSD Oncology, Novartis, Pfizer, and Sanofi; research funding from AstellasPharma, AstraZeneca, Bristol-Myers Squibb, Exelixis,Infinity Pharmaceuticals, Janssen, MSD, and Roche;and travel and accommodations expenses from BristolMyers Squibb, Janssen, Pfizer, and Roche. CL: employment for Chugai (immediate family member); honoraria forPfizer, Astellas, Sanofi, Roche, and Ipsen; consulting/advisory role forAstellas; research funding for Pfizer, Roche, Sanofi, BMS, MSD, and Ipsen(paid to institution); expert testimony for Astellas; travel/accommodation/expenses for Ipsen, Astellas, and Pfizer. RF:Honoraria: Bristol-Myers Squibb, Pfizer, Ipsen, Astellas Pharma, MSD Oncology, Consulting or Advisory Role: Ipsen, Janssen Oncology, Research Funding: Bayer ; LA: grants and honoraria from Pfizer, Novartis, BMS, Ipsen, Roche, AstraZeneca, Amgen, Astellas, Exelixis, Corvus Pharmaceuticals, Peloton therapeutics, MSD and Merck, outside the submitted work. MGG: honoraria for consultancy: BMS, MSD, Ipsen, Pfizer, Eisai;