Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial.

Papillary renal cell carcinoma (PRCC) represents 10%-15% of renal carcinomas. No standard treatments exist for metastatic PRCC (mPRCC) patients. Axitinib is indicated as second-line treatment in metastatic clear cell renal carcinoma, and we aim to assess the efficacy of this vascular endothelial growth factor receptor inhibitor in front line for mPRCC. This French multicentre phase II study AXIPAP enrolled untreated mPRCC patients, with measurable disease, Eastern Cooperative Oncology Group performance status ≤ 1 and adequate organ functions. PRCC had to be confirmed by histology expert central review. Axitinib was administered orally 5 mg twice daily. Primary end-point was progression-free rate at 24 weeks (24w-PFR) by central review. Fifty-six patients were screened, and 44 included (13 type 1, 30 type 2 and 1 non-specified). The median follow-up was 32.0 (13.1-39.9) months. The 24w-PFR was 45.2% (95% confidence interval [CI], 32.6% to +∞), the objective response rate was 28.6% (95% CI, 15.7%-44.6%) (type 1: 7.7%; type 2: 35.7%). The overall median progression free survival was 6.6 months (95% CI, 5.5-9.2), 6.7 months (95% CI, 5.5-9.2) and 6.2 months (95% CI, 5.4-9.2) for type 1 and 2, respectively. Median overall survival was 18.9 months (95% CI, 12.8-not reached). Adverse events were as expected; grade 3-4 treatment-related adverse events were rare except hypertension (27%). Axitinib demonstrated encouraging efficacy in mPRCC patients, especially in type 2 PRCC. Toxicity was manageable. Axitinib appears as an interesting option for first-line treatment and to be worth further investigation in combination with immunotherapy in these patients. Expert pathology review should be recommended in this setting. ClinicalTrials.gov, NCT02489695.

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement Dr. Negrier reports grants, personal fees, non-financial support and other from Pfizer; grants, personal fees and other from Ipsen, during the conduct of the study; personal fees and other from BMS; personal fees from EUSA Pharma; personal fees from Novartis; personal fees from MSD, outside the submitted work. Dr. Rioux-Leclercq reports personal fees from Pfizer and BMS, outside the submitted work, for conferences on non–clear cell renal cell carcinoma and molecular pathways in renal cell carcinoma. Dr. Gross-Goupil reports personal fees and non-financial support from Ipsen; personal fees and non-financial support from Roche; personal fees and non-financial support from MSD; personal fees and non-financial support from BMS; personal fees and non-financial support from Pfizer; non-financial support from Novartis, outside the submitted work. Dr. Gravis reports non-financial support from Pfizer; non-financial support from BMS; non-financial support from Ipsen during the conduct of the study. Dr. Chevreau reports personal fees from Pfizer; personal fees and non-financial support from BMS; personal fees and non-financial support from Ipsen; personal fees and non-financial support from AstraZeneca; personal fees and non-financial support from MSD; personal fees from null, during the conduct of the study; grants from Pfizer, outside the submitted work. Dr. Boyle reports grants and non-financial support from Pfizer, during the conduct of the study; non-financial support from Pfizer; non-financial support from BMS; personal fees and non-financial support from Ipsen; personal fees from Sanofi; non-financial support from Astellas; non-financial support from Jansen, outside the submitted work, Dr. Rolland reports personal fees from Pfizer; personal fees from BMS; personal fees from Ipsen, outside the submitted work; personal fees from Novartis; personal fees from BMS; personal fees and non-financial support from MSD; personal fees and non-financial support from Ipsen, outside the submitted work; Dr. Ravaud reports personal fees and non-financial support from Pfizer; personal fees and non-financial support from BMS; personal fees and non-financial support from Roche; personal fees and non-financial support from Ipsen; personal fees and non-financial support from AstraZeneca; personal fees and non-financial support from MSD, from null, during the conduct of the study; grants from Pfizer outside the submitted work. Dr. Flechon reports honorarium and travel expenses from Pfizer; honorarium and travel expenses from Novartis; honorarium and travel expenses from Ipsen; honorarium and travel expenses from BMS, outside the submitted work. Dr. Albiges reports other from Pfizer; other from Novartis; other from Bristol-Myers Squibb; other from Ipsen; other from Roche; other from MSD; other from AstraZeneca, outside the submitted work. Dr. Pérol reports personal fees and non-financial support from Roche; personal fees and non-financial support from AstraZeneca; grants from MSD AVENIR, outside the submitted work. Dr. Escudier reports grants and personal fees from Pfizer, during the conduct of the study; grants and personal fees from BMS, Roche, Aveo, Novartis, Ipsen, outside the submitted work. Dr. Dermeche, Dr. Geoffrois, Mrs Blanc and Mrs Ferlay declare no competing interests.