Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma

A randomised phase II trial (VINGEM)

Karin Holmsten*, Niels Viggo Jensen, Lene Sonne Mouritsen, Erika Jonsson, Camilla Mellnert, Mads Agerbæk, Cecilia Nilsson, Mette Moe, Andreas Carus, Elisabeth Öfverholm, Outi Lahdenperä, Yvonne Brandberg, Hemming Johansson, Mats Hellström, Hans von der Maase, Helle Pappot, Anders Ullén

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. Patients and methods: Patients with aUC, creatinine clearance 30–60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS). Results: Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44–1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%). Conclusions: The combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. Clinicaltrials.gov number: NCT02665039.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Cancer
ISSN0959-8049
DOI
StatusE-pub ahead of print - 22. okt. 2019

Fingeraftryk

gemcitabine
Carboplatin
Cisplatin
vinflunine
Disease-Free Survival

Citer dette

Holmsten, Karin ; Jensen, Niels Viggo ; Mouritsen, Lene Sonne ; Jonsson, Erika ; Mellnert, Camilla ; Agerbæk, Mads ; Nilsson, Cecilia ; Moe, Mette ; Carus, Andreas ; Öfverholm, Elisabeth ; Lahdenperä, Outi ; Brandberg, Yvonne ; Johansson, Hemming ; Hellström, Mats ; Maase, Hans von der ; Pappot, Helle ; Ullén, Anders. / Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma : A randomised phase II trial (VINGEM). I: European Journal of Cancer. 2019.
@article{4914064fc2864b448bdf1ae0549d3543,
title = "Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM)",
abstract = "Background: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. Patients and methods: Patients with aUC, creatinine clearance 30–60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS). Results: Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95{\%} confidence interval [CI]: 0.44–1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63{\%} versus 40{\%}) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22{\%} versus 3{\%} in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62{\%}, CG 43{\%}), thrombocytopenia (VG 7{\%}, CG 37{\%}) and febrile neutropenia (VG 31{\%}, CG 7{\%}). Conclusions: The combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. Clinicaltrials.gov number: NCT02665039.",
keywords = "Bladder cancer, Carboplatin/gemcitabine, Cisplatin-unfit, Renal impairment, Urothelial carcinoma, Vinflunine, Vinflunine/gemcitabine",
author = "Karin Holmsten and Jensen, {Niels Viggo} and Mouritsen, {Lene Sonne} and Erika Jonsson and Camilla Mellnert and Mads Agerb{\ae}k and Cecilia Nilsson and Mette Moe and Andreas Carus and Elisabeth {\"O}fverholm and Outi Lahdenper{\"a} and Yvonne Brandberg and Hemming Johansson and Mats Hellstr{\"o}m and Maase, {Hans von der} and Helle Pappot and Anders Ull{\'e}n",
year = "2019",
month = "10",
day = "22",
doi = "10.1016/j.ejca.2019.08.033",
language = "English",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Pergamon",

}

Holmsten, K, Jensen, NV, Mouritsen, LS, Jonsson, E, Mellnert, C, Agerbæk, M, Nilsson, C, Moe, M, Carus, A, Öfverholm, E, Lahdenperä, O, Brandberg, Y, Johansson, H, Hellström, M, Maase, HVD, Pappot, H & Ullén, A 2019, 'Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM)', European Journal of Cancer. https://doi.org/10.1016/j.ejca.2019.08.033

Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma : A randomised phase II trial (VINGEM). / Holmsten, Karin; Jensen, Niels Viggo; Mouritsen, Lene Sonne; Jonsson, Erika; Mellnert, Camilla; Agerbæk, Mads; Nilsson, Cecilia; Moe, Mette; Carus, Andreas; Öfverholm, Elisabeth; Lahdenperä, Outi; Brandberg, Yvonne; Johansson, Hemming; Hellström, Mats; Maase, Hans von der; Pappot, Helle; Ullén, Anders.

I: European Journal of Cancer, 22.10.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma

T2 - A randomised phase II trial (VINGEM)

AU - Holmsten, Karin

AU - Jensen, Niels Viggo

AU - Mouritsen, Lene Sonne

AU - Jonsson, Erika

AU - Mellnert, Camilla

AU - Agerbæk, Mads

AU - Nilsson, Cecilia

AU - Moe, Mette

AU - Carus, Andreas

AU - Öfverholm, Elisabeth

AU - Lahdenperä, Outi

AU - Brandberg, Yvonne

AU - Johansson, Hemming

AU - Hellström, Mats

AU - Maase, Hans von der

AU - Pappot, Helle

AU - Ullén, Anders

PY - 2019/10/22

Y1 - 2019/10/22

N2 - Background: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. Patients and methods: Patients with aUC, creatinine clearance 30–60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS). Results: Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44–1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%). Conclusions: The combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. Clinicaltrials.gov number: NCT02665039.

AB - Background: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. Patients and methods: Patients with aUC, creatinine clearance 30–60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS). Results: Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44–1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%). Conclusions: The combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. Clinicaltrials.gov number: NCT02665039.

KW - Bladder cancer

KW - Carboplatin/gemcitabine

KW - Cisplatin-unfit

KW - Renal impairment

KW - Urothelial carcinoma

KW - Vinflunine

KW - Vinflunine/gemcitabine

U2 - 10.1016/j.ejca.2019.08.033

DO - 10.1016/j.ejca.2019.08.033

M3 - Journal article

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -