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 Anti-Cancer Agents & Biologic Therapy
Urothelial Cancers
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.