Advertisement

Real world prospective experience of axitinib in metastatic renal cell carcinoma in a large comprehensive cancer centre

      Highlights

      • Our study reports the efficacy and safety of axitinib in patients with mRCC in routine practice.
      • The results mimick those previously reported in clinical trials.
      • IMDC risk group, grade 3–4 hypertension and dose titration at 2 weeks are associated with better outcome.

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Escudier B.
        • Gore M.
        Axitinib for the management of metastatic renal cell carcinoma.
        Drugs R D. 2011; 11: 113-126https://doi.org/10.2165/11591240-000000000-00000
        • Motzer R.J.
        • Escudier B.
        • McDermott D.F.
        • George S.
        • Hammers H.J.
        • Srinivas S.
        • et al.
        Nivolumab versus everolimus in advanced renal-cell carcinoma.
        N Engl J Med. 2015; 373: 1803-1813https://doi.org/10.1056/NEJMoa1510665
        • Choueiri T.K.
        • Escudier B.
        • Powles T.
        • Mainwaring P.N.
        • Rini B.I.
        • Donskov F.
        • et al.
        Cabozantinib versus everolimus in advanced renal-cell carcinoma.
        N Engl J Med. 2015; 373: 1814-1823https://doi.org/10.1056/NEJMoa1510016
        • Rini B.I.
        • Escudier B.
        • Tomczak P.
        • Kaprin A.
        • Szczylik C.
        • Hutson T.E.
        • et al.
        Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.
        Lancet. 2011; 378: 1931-1939https://doi.org/10.1016/S0140-6736(11)61613-9
        • Motzer R.J.
        • Escudier B.
        • Tomczak P.
        • Hutson T.E.
        • Michaelson M.D.
        • Negrier S.
        • et al.
        Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 552-562https://doi.org/10.1016/S1470-2045(13)70093-7
        • Katabathina V.S.
        • Lassau N.
        • Pedrosa I.
        • Ng C.S.
        • Prasad S.R.
        Evaluation of treatment response in patients with metastatic renal cell carcinoma: role of state-of-the-art cross-sectional imaging.
        Curr Urol Rep. 2012; 13: 70-81https://doi.org/10.1007/s11934-011-0233-x
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • Schwartz L.H.
        • Sargent D.
        • Ford R.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247https://doi.org/10.1016/j.ejca.2008.10.026
        • Lin D.
        • Wei L.
        • Ying Z.
        Checking the Cox model with cumulative sums of martingale-based residuals.
        Biometrika. 1993; 80: 557-572https://doi.org/10.1093/biomet/80.3.557
        • Heinze G.
        • Puhr R.
        Bias-reduced and separation-proof conditional logistic regression with small or sparse data sets.
        Stat Med. 2010; 29: 770-777https://doi.org/10.1002/sim.3794
        • Halimi J.-M.
        • Azizi M.
        • Bobrie G.
        • Bouché O.
        • Deray G.
        • des Guetz G.
        • et al.
        Vascular and renal effects of anti-angiogenic therapy.
        Néphrologie Thérapeutique. 2008; 4: 602-615https://doi.org/10.1016/j.nephro.2008.10.002
        • Rini B.I.
        • Cohen D.P.
        • Lu D.R.
        • Chen I.
        • Hariharan S.
        • Gore M.E.
        • et al.
        Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib.
        J Natl Cancer Inst. 2011; 103: 763-773https://doi.org/10.1093/jnci/djr128
        • Rini B.I.
        • Schiller J.H.
        • Fruehauf J.P.
        • Cohen E.E.W.
        • Tarazi J.C.
        • Rosbrook B.
        • et al.
        Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors.
        Clin Cancer Res. 2011; 17: 3841-3849https://doi.org/10.1158/1078-0432.CCR-10-2806
        • Mizuno R.
        • Kosaka T.
        • Mikami S.
        • Oya M.
        Efficacy of axitinib in patients with metastatic renal cell carcinoma previously treated with both VEGFR-TKI and mTORI.
        ASCO Meet Libr. 2014; (doi:J Clin Oncol 32, 2014 (suppl; abstr e15585))
        • MacLean E.A.
        • Mehle K.
        • Eremina D.
        • Quigley J.M.
        Retrospective study of real world axitinib use in the United States.
        J Clin Oncol. 2014; 32 (ASCO Meet Libr 2014) (suppl; abstr e15576)
        • MacLean E.
        • Cisar L.
        • Mehle K.
        • Eremina D.
        • Quigley J.M.
        Real-world axitinib use in the United States: a retrospective study using linked datasets.
        J Manag Care Spec Pharm. 2016; 22 (723–732u)https://doi.org/10.18553/jmcp.2016.22.6.723
        • D'Aniello C.
        • Vitale M.G.
        • Farnesi A.
        • Calvetti L.
        • Laterza M.M.
        • Cavaliere C.
        • et al.
        Axitinib after sunitinib in metastatic renal cancer: preliminary results from Italian “Real-World” SAX study.
        Front Pharmacol. 2016; 7: 331https://doi.org/10.3389/fphar.2016.00331
        • Rini B.I.
        • Melichar B.
        • Ueda T.
        • Grünwald V.
        • Fishman M.N.
        • Arranz J.A.
        • et al.
        Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial.
        Lancet Oncol. 2013; 14: 1233-1242https://doi.org/10.1016/S1470-2045(13)70464-9
        • Eto M.
        • Uemura H.
        • Tomita Y.
        • Kanayama H.
        • Shinohara N.
        • Kamei Y.
        • et al.
        Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma.
        Cancer Sci. 2014; 105: 1576-1583https://doi.org/10.1111/cas.12546
        • Thiam R.
        • Fournier L.S.
        • Trinquart L.
        • Medioni J.
        • Chatellier G.
        • Balvay D.
        • et al.
        Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib.
        Ann Oncol. 2010; 21: 936-941https://doi.org/10.1093/annonc/mdp466
        • Ishihara H.
        • Yagisawa T.
        • Kondo T.
        • Omae K.
        • Takagi T.
        • Iizuka J.
        • et al.
        Effect of the timing of best tumor shrinkage on survival of patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitor therapy.
        Int J Clin Oncol. 2017; 22: 126-135https://doi.org/10.1007/s10147-016-1032-7
        • Krajewski K.M.
        • Franchetti Y.
        • Nishino M.
        • Fay A.P.
        • Ramaiya N.
        • Van den Abbeele A.D.
        • et al.
        10% Tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study.
        Oncologist. 2014; 19: 507-514https://doi.org/10.1634/theoncologist.2013-0391
        • Grünwald V.
        • Lin X.
        • Kalanovic D.
        • Simantov R.
        Early tumour shrinkage: a tool for the detection of early clinical activity in metastatic renal cell carcinoma.
        Eur Urol. 2016; 70: 1006-1015https://doi.org/10.1016/j.eururo.2016.05.010
        • Rini B.I.
        • Tomita Y.
        • Melichar B.
        • Ueda T.
        • Grünwald V.
        • Fishman M.N.
        • et al.
        Overall survival analysis from a randomized phase II study of axitinib with or without dose titration in first-line metastatic renal cell carcinoma.
        Clin Genitourin Cancer. 2016; 14: 499-503https://doi.org/10.1016/j.clgc.2016.04.005