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., NCT02489695.

European journal of cancer (Oxford, England : 1990). 2020 Mar 05 [Epub ahead of print]

Sylvie Negrier, Nathalie Rioux-Leclercq, Céline Ferlay, Marine Gross-Goupil, Gwenaëlle Gravis, Lionel Geoffrois, Christine Chevreau, Helen Boyle, Frederic Rolland, Ellen Blanc, Alain Ravaud, Slimane Dermeche, Aude Flechon, Laurence Albiges, David Pérol, Bernard Escudier, GETUG collaborative group

Univ Lyon, Claude Bernard University Lyon 1, Medical Oncology, Léon Bérard Cancer Centre, Lyon, France. Electronic address: ., Department of Pathology, University Hospital Centre of Pontchaillou, Rennes, France., Department of Clinical Research and Innovation, Léon Bérard Cancer Centre, Lyon, France., Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Medical Oncology, Paoli Calmettes Institute, Marseille, France., Medical Oncology, Institute of Cancerology of Lorraine - Alexis Vautrin, Vandoeuvre Les Nancy, France., Medical Oncology, University Institute of Cancer, Toulouse- Oncopole, Toulouse, France., Medical Oncology, Léon Bérard Cancer Centre, Lyon, France., Medical Oncology, Institute of Cancer Research in Western France, René Gauducheau Cancer Centre, Saint-Herblain, France., Medical Oncology, Gustave Roussy, Villejuif, France.