Margarida Matias1, Gwénaël Le Teuff2, Laurence Albiges3, Annalisa Guida4, Caroline Brard5, Giulia Bacciarelo6, Yohann Loriot7, Christophe Massard8, Nathalie Lassau9, Karim Fizazi10, Bernard Escudier11. 1. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: margarida.matias@gustaveroussy.fr. 2. Department of Biostatistics and Epidemiology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France; Université Paris-Saclay, University of Paris-Sud, UVSQ, CESP, INSERM, Villejuif, F-94085, France. Electronic address: gwenael.leteuff@gustaveroussy.fr. 3. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: laurence.albiges@gustaveroussy.fr. 4. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: guida.annalisa@hotmail.it. 5. Department of Biostatistics and Epidemiology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France; Université Paris-Saclay, University of Paris-Sud, UVSQ, CESP, INSERM, Villejuif, F-94085, France. Electronic address: caroline.brard@gustaveroussy.fr. 6. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: giulia.baciarello@gustaveroussy.fr. 7. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: yohann.loriot@gustaveroussy.fr. 8. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: christophe.massard@gustaveroussy.fr. 9. Department of Imaging and IR4M UMR808, Gustave Roussy, F-94805, Villejuif, France; Université Paris-Sud, IR4M UMR808, Villejuif, F-94085, France. Electronic address: nathalie.lassau@gustaveroussy.fr. 10. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr. 11. Department of Medical Oncology, Gustave Roussy, F-94805, Villejuif, France. Electronic address: bernard.escudier@gustaveroussy.fr.
Abstract
BACKGROUND: Axitinib has shown activity in metastatic renal cell carcinoma (mRCC) in a large phase III clinical trial and was approved in patients who failed first-line therapy. This drug has been available in France since November 2012. The objective is to report efficacy and safety of axitinib in mRCC outside of clinical trials. METHODS: A prospective evaluation of mRCC patients treated by axitinib in second or further next-line therapy at Gustave Roussy was conducted from 2012 to 2015. Objective response rate (ORR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and toxicities were analysed. The correlation between clinical markers and ORR, PFS, TTF and OS were explored. RESULTS: One-hundred and sixty patients with mRCC, received axitinib in second (40%) or further next-line therapy (60%). International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification was good, intermediate and poor in 13%, 54% and 32%, respectively. Dose titration (DT) to 7 mg twice a day (bid) was performed in 38% and to 10 mg bid in 19% of the patients. Hypertension was the most common adverse event, (grade (G)3: 39%; G4: 2%). ORR occurred in 32% (n = 33, only partial response). Median PFS, TTF and OS were 8.3, 5.8 and 16.4 months, respectively. IMDC risk group and DT at 2 weeks are associated to ORR while grade 3 hypertension is marginally associated. IMDC risk group and grade 3 hypertension are significantly associated with better PFS, TTF and OS while DT at 2 weeks is associated to PFS and TTF. CONCLUSION: Efficacy of axitinib in routine practice is similar to that previously reported, not only in second- but also in further next-lines of therapy.
BACKGROUND:Axitinib has shown activity in metastatic renal cell carcinoma (mRCC) in a large phase III clinical trial and was approved in patients who failed first-line therapy. This drug has been available in France since November 2012. The objective is to report efficacy and safety of axitinib in mRCC outside of clinical trials. METHODS: A prospective evaluation of mRCC patients treated by axitinib in second or further next-line therapy at Gustave Roussy was conducted from 2012 to 2015. Objective response rate (ORR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and toxicities were analysed. The correlation between clinical markers and ORR, PFS, TTF and OS were explored. RESULTS: One-hundred and sixty patients with mRCC, received axitinib in second (40%) or further next-line therapy (60%). International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification was good, intermediate and poor in 13%, 54% and 32%, respectively. Dose titration (DT) to 7 mg twice a day (bid) was performed in 38% and to 10 mg bid in 19% of the patients. Hypertension was the most common adverse event, (grade (G)3: 39%; G4: 2%). ORR occurred in 32% (n = 33, only partial response). Median PFS, TTF and OS were 8.3, 5.8 and 16.4 months, respectively. IMDC risk group and DT at 2 weeks are associated to ORR while grade 3 hypertension is marginally associated. IMDC risk group and grade 3 hypertension are significantly associated with better PFS, TTF and OS while DT at 2 weeks is associated to PFS and TTF. CONCLUSION: Efficacy of axitinib in routine practice is similar to that previously reported, not only in second- but also in further next-lines of therapy.
Authors: James I Geller; Elizabeth Fox; Brian K Turpin; Stuart L Goldstein; Xiaowei Liu; Charles G Minard; Rachel A Kudgus; Joel M Reid; Stacey L Berg; Brenda J Weigel Journal: Cancer Date: 2018-11-05 Impact factor: 6.860