Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial
- PMID: 32146304
- DOI: 10.1016/j.ejca.2020.02.001
Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial
Abstract
Introduction: 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.
Methods: 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.
Results: 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%).
Conclusions: 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.
Clinical trial registration: ClinicalTrials.gov, NCT02489695.
Keywords: Advanced renal cancer; Papillary renal cell carcinoma; Targeted therapy; Tyrosine kinase; VEGF inhibitor; Vascular endothelial growth factor.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Conflict of interest statement
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.
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