Abstract 724P
Background
Renal medullary carcinoma (RMC) and collecting duct carcinoma (CDC) account for < 3% of kidney cancers. They share clinico-pathologic features and have a poor prognosis. First-line metastatic treatment is based on a gemcitabine + platinum (GC) regimen. Retrospective data suggest progression-free survival (PFS) increased with the addition of bevacizumab (bev). We prospectively assessed the safety and efficacy of GC + bev in metastatic RMC/CDC.
Methods
UNICANCER designed a national phase 2 open-label trial in 18 centres in France. Patients (pts) with metastatic RMC/CDC and no prior systemic treatment were eligible. A central pathological review was performed before starting treatment. Pts received bev 15 mg/kg on day 1 (D1) + gemcitabine 1.250 mg/m2 on D1, D8 + cisplatin 70 mg/m2 or carboplatin AUC5 on D1 every 3 weeks up to 6 cycles. Pts with no progressive disease after 6 cycles continued bev alone until progression or toxicity. The co-primary endpoints were: objective response rate (ORR) and PFS at 6 months (ORR-6; PFS-6). The rule to declare the treatment effective was at least 15 pts with a positive ORR-6 or 25 pts with positive PFS-6.
Results
From Feb 2015 to Jan 2019, 34 pts were enrolled (3 with RMC and 26 with CDC, 5 unknown). At interim analysis, the IDMC closed the trial for toxicity. After a 25-month median follow-up, the ORR-6 was 29% (10/34) and the PFS-6 was 41% (14/34). The overall ORR was 39% (1 complete response, 12 partial responses). The median overall survival was 11 months (7-15). Overall, 25 pts (73%) completed the 6 cycles. Seven pts discontinued bev because of hypertension (3), proteinuria (3), or colonic perforation (1). Five pts stopped chemotherapy due to haematological (3 with carboplatin) or renal toxicity (2 with cisplatin). Grade 3–4 toxicities were reported in 28/34 pts (82%); the most common toxicities were haematological (20/34) and hypertension (5/34). Two pts had grade 5 toxicity: a subdural hematoma after C1 and encephalopathy after 5 months of treatment.
Conclusions
The study did not meet its co-primary endpoints. Based on the observed toxicity of the combination, a GC regimen without the addition of bev remains the standard treatment for patients with RMC/CDC.
Clinical trial identification
NCT02363751.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Roche.
Disclosure
C. Thibault: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Ipsen. A. Fléchon: Honoraria (self), Travel/Accommodation/Expenses: Roche. L. Albiges: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: BMS; Advisory/Consultancy: Ipsen; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZenenca; Advisory/Consultancy: Merck; Advisory/Consultancy: Amgen; Advisory/Consultancy: Astellas; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Corvus Pharmaceuticals; Advisory/Consultancy: Peloton therapeutics. C. Joly: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Janssen. P. Barthélémy: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Cilag; Honoraria (self), Advisory/Consultancy: EusaPharma; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Honoraria (self): Astellas; Travel/Accommodation/Expenses: Ipsen. M. Gross Goupil: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Merck GA; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: BMS. C.M. Chevreau: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. F. Joly: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche ; Speaker Bureau/Expert testimony: Novartis ; Speaker Bureau/Expert testimony: Pfizer ; Speaker Bureau/Expert testimony: GSK ; Speaker Bureau/Expert testimony: BMS ; Speaker Bureau/Expert testimony: MSD ; Speaker Bureau/Expert testimony: IPSec ; Speaker Bureau/Expert testimony: Janssen ; Speaker Bureau/Expert testimony: Sanofi. B. Laguerre: Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): AstraZenenca; Travel/Accommodation/Expenses: Pfizer. G. Gravis: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution): Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. M-O. Timsit: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen. N. Pecuchet: Full/Part-time employment: Dassault Systèmes. S. Oudard: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Sanofi. All other authors have declared no conflicts of interest.