No Progression-Free Survival Difference With First-Line Axitinib vs Sorafenib in Metastatic Renal Cell Carcinoma


Key Points

  • There was no significant difference in progression-free survival with axitinib vs sorafenib as first-line treatment.
  • Axitinib was associated with prolonged progression-free survival in patients with ECOG performance status of 0 and in patients with prior nephrectomy. 
  • The objective response rate was greater with axitinib.

In a phase III trial reported in The Lancet Oncology, Thomas E. Hutson, DO, PharmD, of Baylor Sammons Cancer Center and colleagues compared the second-generation VEGFR inhibitor axitinib (Inlyta) with sorafenib (Nexavar) as first-line treatment of metastatic renal cell carcinoma. There was no significant difference between groups in progression-free survival, but axitinib was associated with clinical activity and an acceptable toxicity profile.  

Study Details

In this open-label international trial, 288 patients with treatment-naive measurable clear-cell metastatic renal cell carcinoma were randomly assigned 2:1 to receive axitinib at 5 mg twice daily (n = 192) or sorafenib at 400 mg twice daily (n = 96). Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status. The primary endpoint was progression-free survival assessed by an independent review committee. The trial is ongoing.

The axitinib and sorafenib groups were generally well balanced for age (median, 58 years in both), ethnicity/race (white in 71% and 69%), ECOG performance status (0 in 57% in both, 1 in 43% in both), previous nephrectomy (85% and 90%), Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (favorable in 49% and 55%, intermediate in 44% and 42%), and sites of metastasis (lung in 71% and 75%, lymph nodes in 52% and 57%). The greatest enrollment was from Ukraine (n = 61), Russia (n = 58), and India (n = 34), with patients being enrolled in 10 additional countries.

No Progression-Free Survival Difference

As of a data cutoff date of July 27, 2012, when 59% of patients had died or had disease progression, there was no difference in median progression-free survival between the axitinib group and the sorafenib group (10.1 vs 6.5 months, stratified hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.56–1.05, one-sided P = .038).

In a prespecified analysis, median progression-free survival was longer with axitinib in patients with ECOG performance status of 0 (13.7 vs 6.6 months, unstratified HR = 0.64, 95% CI = 0.42–0.99, one-sided P = .022), but not in patients with ECOG performance status of 1 (6.5 vs 6.4 months, unstratified HR = 0.93, 95% CI = 0.59–1.48, one-sided P = .38). There were no significant differences between groups in other subgroup analyses, with hazard ratios nonsignificantly favoring axitinib in analysis according to ethnic subgroups, sex, age, and MSKCC risk group. Median progression-free survival was also longer with axitinib in a post hoc analysis among 250 patients with previous nephrectomy (10.3 vs 6.4 months, unstratified HR = 0.67, 95% CI = 0.47–0.93, one-sided P = .009).

The objective response rate was significantly higher in the axitinib group (32% vs 15%, all partial responses, risk ratio = 2.21, 95% CI = 1.31–3.75, stratified one-sided P = .0006). Median durations of response were 14.7 months (95% CI = 11.0 months–not estimable) and 14.3 months (11.3 months–not estimable).

Toxicity Profiles

Adverse events of any grade that were more common with axitinib (≥ 10% difference) were diarrhea (50% vs 40%), hypertension (49% vs29%), weight decrease (37% vs 24%), decreased appetite (29% vs19%), dysphonia (23% vs10%), hypothyroidism (21% vs 7%), and upper abdominal pain (16% vs 6%), whereas those more common with sorafenib were palmar-plantar erythrodysesthesia (39% vs 26%), rash (20% vs 10%), alopecia (19% vs 4%), and erythema (19% vs 3%).

The most common grade 3 or 4 adverse events in axitinib patients were hypertension (14% vs 1%), diarrhea (9% vs 5%), asthenia (8% vs 5%), and weight decrease (8% vs 3%); the most common grade 3 or 4 adverse events in sorafenib patients were palmar-plantar erythrodysesthesia (16% vs 7%), diarrhea, and asthenia.

Serious adverse events occurred in 34% of the axitinib group and 25% of the sorafenib group. Adverse events led to dose interruption in 50% of axitinib patients and 46% of sorafenib patients, with 3% and 2% discontinuing treatment due to treatment-related adverse events.

The investigators concluded: “To our knowledge, this is the first randomised phase III trial comparing axitinib with an active agent in the first-line setting. Although there was no significant difference between patient groups’ progression-free survival, axitinib showed clinical activity and an acceptable safety profile as first-line therapy for patients with treatment-naïve metastatic renal-cell carcinoma. Given that no therapy is curative for patients with this disease, continuing research is needed to identify new active drugs.”

The study was funded by Pfizer Inc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.