793PD - Axitinib vs sorafenib for advanced renal cell carcinoma: phase III overall survival results and analysis of prognostic factors

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, non-prostate (renal cancer)
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Robert Motzer
Authors R.J. Motzer1, B. Escudier2, P. Tomczak3, S. Negrier4, M.E. Gore5, J. Tarazi6, S. Hariharan7, B. Rosbrook6, S. Kim6, B.I. Rini8
  • 1Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York/US
  • 2Institut Gustave Roussy, FR-94805 - Villejuif/FR
  • 3Uniwersytet Medyczny, Klinika Onkologii, Poznań/PL
  • 4Dept. Of Oncology, Centre Léon Bérard, FR-69008 - Lyon/FR
  • 5Department Of Medicine, Royal Marsden Hospital NHS Foundation Trust, GB-SW3 6JJ - London/UK
  • 6Pfizer Oncology, Pfizer Oncology, San Diego/US
  • 7Pfizer Inc, Pfizer Inc, New York/US
  • 8Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Taussig Cancer Institute, Cleveland/US

Abstract

Purpose

In the phase III AXIS trial, axitinib prolonged progression-free survival (PFS) compared with sorafenib as 2nd-line therapy for metastatic renal cell carcinoma (mRCC) (Lancet 2011;378:1931). Mature overall survival (OS) data (as of Nov 1, 2011) are reported.

Methods

723 patients (pts) with clear cell mRCC, progressive disease after 1 systemic therapy, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 were stratified by ECOG PS and prior therapy and randomised 1:1 to axitinib 5 mg twice daily (BID) or sorafenib 400 mg BID. OS was analysed as a secondary endpoint based on 425 events and compared using a 1-sided log-rank test stratified by ECOG PS and prior therapy. Pretreatment prognostic factors were studied by multivariate analyses. Pts were grouped by diastolic blood pressure (dBP) on therapy (≥1 dBP measurement ≥90 vs dBP <90 mmHg) and OS was evaluated.

Results

Median OS (mOS) was 20.1 mo (95% confidence interval [CI]16.7, 23.4) in the axitinib arm and 19.2 mo (95% CI 17.5, 22.3) in the sorafenib arm; hazard ratio (HR) 0.969 (95% CI 0.800, 1.174); P = 0.3744. In prior therapy subsets, mOS with axitinib vs sorafenib was: prior cytokine, 29.4 vs 27.8 mo (HR 0.813; 95% CI 0.555, 1.191); prior sunitinib, 15.2 vs 16.5 mo (HR 0.997; 95% CI 0.782, 1.270); prior bevacizumab plus interferon-α, 14.7 vs 19.8 mo (HR 1.825; 95% CI 0.942, 3.535); and prior temsirolimus, 14.0 vs 8.5 mo (HR 0.459; 95% CI 0.165, 1.278). Prognostic factors for longer OS with 2nd-line therapy (P < 0.01) included type of prior therapy, ECOG PS = 0, no bone metastases, elevated haemoglobin, and low corrected calcium. In a 12-week landmark analysis, mOS was significantly longer in the dBP ≥90 mmHg group (axitinib arm: 20.7 vs 12.9 mo, HR 0.725, P = 0.014; sorafenib arm: 20.9 vs 14.8 mo, HR 0.657, P = 0.002). 56% of patients who discontinued treatment received subsequent therapy.

Conclusions

Axitinib resulted in prolonged PFS and similar OS compared with sorafenib for 2nd-line mRCC. OS results and prognostic factors may be used in clinical trial design for novel agents in 2nd-line therapy.

Disclosure

R.J. Motzer: Pfizer Consultant. Research Funding from Pfizer.

B. Escudier: Advisory role for Novartis, Bayer, Pfizer, Aveo, GSK.

S. Negrier: Ad Board : Pfizer Honoraria: Novartis Research grants: GSK, Roche.

M.E. Gore: Speaker bureau and advisory boards: Roche, GSK, Novartis, Bayer, Pfizer, Schering Plough, Bristol Myers Squibb, Aveo, AstraZeneca, Astellas.

J. Tarazi: Employee of and own stock in Pfizer.

S. Hariharan: Employee of and own stock in Pfizer.

B. Rosbrook: Employee of and own stock in Pfizer.

S. Kim: Employee of and own stock in Pfizer.

B.I. Rini: Consulting and research funding from Pfizer.

All other authors have declared no conflicts of interest.