812PD - Mature survival (OS) data of a randomised international phase II trial (JASINT1): Vinflunine (VFL)-gemcitabine (GEM) vs. VFL-CBDCA in CDDP-unfit pa...

Date 29 September 2014
Event ESMO 2014
Session Genitourinary tumours, non prostate
Topics Anticancer agents
Urothelial Cancers
Therapy
Biological Therapy
Presenter Maria De Santis
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors M. De Santis1, P.J. Wiechno2, C. Lucas3, C. Lin4, W. Su5, J. Bellmunt6, K. Legrand7, R. Fougeray7, S. Culine8
  • 13rd Medical Department, LBI-ACR VIEnna and KFJ-Hospital, 1100 - Wien/AT
  • 2Department Of Uro-oncology, Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie, Warsaw/PL
  • 3Medical Affairs Oncology, Institute de Recherche Pierre Fabre, 92654 - Boulogne-Billancourt/FR
  • 4Department Of Oncology, National Taiwan University Hospital, Tapei/TW
  • 5Oncology, National Cheng Kung University Hospital, 70403 - Tainan/TW
  • 6Medical Oncology, Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston/US
  • 7Biometry Department, Institut de Recherche Pierre Fabre, Boulogne-Billancourt/FR
  • 8Oncology, Hospital Saint Louis, 75475 - PARIS CEDEX/FR

Abstract

Aim

There is no standard 1st line chemotherapy (CT) for advanced or metastatic UC in pts unfit for a CDDP-based regimen. VFL, an EMA approved agent in the post-platinum setting has shown to be safe in pts with renal impairment. The study aimed to assess the benefit/risk ratio of 2 VFL-based CT regimens in UC.

Methods

Pts with a creatinine clearance (CrCl) <60mL/min but ≥30, PS 0/1, no prior systemic CT (except neoadjuvant or adjuvant CT if relapse occurred ≥6 mo after last dose) were randomized. Based on the CrCl, <40 or ≥40mL/min, pts received q 21 days (D) VFL 250 or 280mg/m2, plus GEM (Arm A) 750mg/m2 D1&8 escalated to 1000 cycle 2 (if no toxicity Grade (G) ≥2) or plus CBDCA AUC 4.5 D1 (Arm B). The primary endpoint was the disease control rate (DCR = CR + PR + SD). With α =5%, ß =20%, 31 evaluable pts/arm were planned to detect in each arm an improvement of 22% compared to H0 (41%). Safety, PFS and OS were secondary endpoints.

Results

69 pts (34 arm A, 35 arm B) were enrolled over 18 months: at the median (med) follow-up of 25.9 mo 74% pts had died. Pts characteristics were similar in both groups: med age 70 yrs; PS 0 / 1 in 42% / 58%; primary sites: 52% bladder and 46% upper tract; visceral mets 49%, med CrCl 46mL/min. Med number of cycles was 5 (A) and 4 (B). More haematological G3/4 adverse events (AE) were reported in arm B: neutropenia in 68% (vs 38%) and febrile neutropenia in 14% (vs 3%) of pts. Main non-haematological G3/4 AE were fatigue (21.7%), infection (7.2%), and constipation (4.3%) without major difference between arms. DCR was 77% in both groups; ORR was 44.1% vs 28.6%, med PFS 5.9 vs 6.1 mo and med OS 14.0 vs 12.8 mo in arms A and B, respectively. Cause of death: progression in 90%, 1 drug-related AE (B), other reasons in 8%. Further anticancer drugs: 59% (A) and 51% (B); CBDCA, GEM and paclitaxel in 23%, 29% and 30%, respectively, with more taxanes in arm A (35%) and more GEM in arm B (37%).

Conclusions

Both VFL doublets are feasible with a similar DCR. However, a higher ORR and OS, while showing less haematological toxicity, favour VFL-GEM which warrants further clinical study.

Disclosure

M. De Santis: Advisory board: Laboratoire Pierre Fabre Corporate-sponsored research: Laboratoire Pierre Fabre Consultancy: Laboratoire Pierre Fabre; C. Lucas: Pierre Fabre employee; J. Bellmunt: Advisory board member of Laboratoires Pierre Fabre; K. Legrand and R. Fougeray: Laboratoires Pierre Fabre employee; S. Culine: Advisory board member and consultancies for Laboratoires Pierre Fabre. All other authors have declared no conflicts of interest.