ORLANDO – Compared with sorafenib, axitinib as first-line therapy was associated with a 3.6 month improvement in progression-free survival among patients with metastatic renal cell carcinoma.
The median PFS was 10.1 months in the axitinib arm and 6.5 months in the sorafenib arm. (hazard ratio, 0.77; one-sided P = .038). The results did not reach the predetermined significance level of 0.025, and hence the trial didn’t achieve its primary endpoint, said Dr. Thomas E. Hutson at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
Dr. Thomas E. Hutson
No differences in overall survival data have been noted to date in the ongoing phase III trial. Dr. Hutson of Texas Oncology – Baylor Charles A. Sammons Cancer Center, Dallas, and the study’s lead author, said that researchers are waiting for the survival data to mature.
Axitinib is a vascular endothelial growth factor receptor inhibitor that is approved for advanced renal cell carcinoma (RCC) after one prior systemic therapy has failed.
To examine the value of axitinib as a first-line therapy, researchers took into account results from previous clinical trials (J. Clin. Oncol. 2009; 27:1280-9) and amended an ongoing randomized trial of second-line axitinib vs. sorafenib to include a population of first-line therapy patients.
The Pfizer-sponsored multicenter, randomized, open-label, phase III trial included 288 untreated patients with clear-cell mRCC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomized 2:1 to axitinib (5 mg, twice daily) or to sorafenib (400 mg, twice daily.) The randomization was stratified by ECOG performance status.
The primary endpoint was progression-free survival (PFS) as determined by an independent radiology committee. The study had a 90% power to detect a 78% improvement in PFS.
Secondary endpoints included overall survival, objective response rate, safety, duration of response, kidney cancer–specific symptoms, and health-related quality of life.
Patients’ baseline characteristics were well balanced between the two arms, and median patient age was 58 years old. ECOG performance status was 0 for 57% and 1 for 43%. Nephrectomies were performed in 85% of patients in the axitinib arm and 90% in the sorafenib arm. About 14% of the patients were from North America.
Patients who had a nephrectomy and an ECOG performance status of 0 faired better if they were in the axitinib arm. Among patients who had a nephrectomy, axitinib-treated patients had a median PFS of 10.3 months and sorafenib-treated patients had a median PFS of 6.4 months (HR, 0.67*; one-sided P = .009). Patients with an ECOG performance status of 0 had a median PFS of 13.7 months in the axitinib arm and 6.6 months in the sorafenib arm (HR, 0.644; one-sided P =.022). Patients with an ECOG performance status of 1 had similar median PFS – 6.5 months in the axitinib arm and 6.4 months in sorafenib arm.
Objective response rate was 32.3% with axitinib and 14.6% with sorafenib.
Patients in the axitinib arm had more hypertension and diarrhea (49% vs. 29% with sorafenib, and 50% vs. 40% with sorafenib.) Palmar-plantar erythrodysesthesia was more common with sorafenib (39% vs. 26% with axitinib).
Dr. Hutson has been a consultant or adviser for, and has received honoraria and research funding from AVEO, Bayer, GlaxoSmithKline, Novartis, and Pfizer, the maker of axitinib.
*Correction, 4/17/2013: An earlier version of this story misstated the HR value in patients who had nephrectomy.