AXIS 1032: Axitinib associated with extended PFS in metastatic RCC

Issue: July 10, 2011

2011 ASCO Annual Meeting

In a randomized, phase 3 trial, axitinib was associated with an additional 2 months of PFS compared with sorafenib in patients with clear-cell advanced renal cell carcinoma.

In results from the international AXIS 1032 trial scheduled to be presented June 6 at the 2011 ASCO Annual Meeting, median PFS was 6.7 months (95% CI, 6.3-8.6) for patients assigned to axitinib (Pfizer) vs. 4.7 months (95% CI, 4.6-5.6) for patients assigned to sorafenib (Nexavar, Bayer; HR=0.665).

Brian I. Rini, MD, associate professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and director for clinical research at the Cleveland Clinic Taussig Cancer Institute, told HemOnc Today before the meeting that although there have been several drugs recently approved to treat metastatic kidney cancer, those drugs have only been tested against placeboes. This is the first trial comparing two kidney cancer drugs against each other.

“We’ve been lacking active comparisons to determine whether one drug is better than another in a given setting,” Rini said. “Hopefully, this is a trial that takes along a road to actually build effective sequences of therapies for patients.”

There were 723 patients from the US, European Union and Japan included in the study. Patients were stratified by performance status, then assigned to the selective VEGF inhibitor axitinib (n=361) or 400 mg daily sorafenib (n=362). Patients in the axitinib group were assigned to a starting daily dose of 5 mg. Dosage was increased to 7 mg, then to 10 mg as tolerated.

More than half of the cohort (54%) had undergone previous treatment with sunitinib (Sutent, CPPI CV), 35% with cytokines, 8% with bevacizumab (Avastin, Genentech) and 3% with temsirolimus-based (Torisel, Wyeth) regimens.

PFS was also superior in the axitinib group for patients who underwent treatment with cytokines (12.1 months vs. 6.5 months) and who underwent treatment with sunitinib (4.8 months vs. 3.4 months). Objective response rate was 19.4% for axitinib compared with 9.4% for sorafenib.

The safety profile for axitinib was different but not necessarily better than that of sorafenib. Hypertension (40% vs. 29%), fatigue (39% vs. 32%), dysphonia (31% vs. 14%) and hypothyroidism (19% vs. 8%) were more common in patients assigned to axitinib. Patients assigned to sorafenib were more likely to experience hand-foot syndrome (27% vs. 51%), rash (13% vs. 32%), alopecia (4% vs. 32%) and anemia (4% vs. 12%).

Rini said, taken on its own, 2 additional months of PFS is of limited value. But quality-of-life results collected in a companion study scheduled to be presented by David Cella, PhD, also show that the delay in progression was accompanied by a delay in quality-of-life deterioration.

“If all we’re doing is just waiting another 2 months for patients’ scans to worsen, I think one could argue the clinical utility of that is small,” Cella said. “But axitinib actually delays patients from feeling worse.”

In the quality-of-life study, patients were asked to fill out a Functional Assessment of Cancer Therapy-Kidney Symptom Index and its disease-related symptoms subscale questionnaires at baseline, every 4 weeks while on study, at end of study treatment/withdrawal and 28 days after last dose. The primary endpoint was time to deterioration, a composite endpoint of death, progression or symptom worsening.

Axitinib was associated with a 25% reduction in risk for deterioration compared with sorafenib. Cella, chair of the department of medical social sciences at Northwestern University Feinberg School of Medicine, said the results of this companion study add value to the PFS findings.

“If patient’s symptoms got worse, even if their cancer didn’t progress, we counted that as an event. Instead of just looking at progression, we added symptom worsening,” he said. “When we did that, we found axitinib was still superior. There’s no counteracting toxicity difference for axitinib compared to sunitinib. The value of PFS is supported by this follow-up analysis.” – by Jason Harris

For more information:

Cella D. #4504.

Rini BI. #4503. Presented at: 2011 ASCO Annual Meeting; Chicago; June 3-7, 2011.

Disclosures: Dr. Rini reported receiving consulting fees from AVEO, GlaxoSmithKline and Pfizer, and research funding from GlaxoSmithKline and Pfizer. Dr. Cella reported receiving research funding, consulting fees and honoraria from Pfizer, Novartis, Bayer and AVEO.

There clearly appeared to be a time to progression advantage for axitinib vs. sorafenib, but we don’t know the cost differential. Any clinician has to take that into consideration these days. The toxicity profiles were a little different between the two drugs. As a clinician, that gives me some backup — if there is a toxicity problem with one drug, I can switch to the other. Is axitinib a huge breakthrough in my armamentarium? Not really.

When looking at time to deterioration, that could represent a difference reflected in the quality-of-life tool. Or it could represent a difference in time to progression or time to death. It’s not clear to me whether there was a significant difference in the patient-reported outcomes between the two drugs so much as there was a 2-month difference in time to progression. I’d like to see more information about time to deterioration. That calculation included more than just the patient-reported outcomes. The quality-of-life data are interesting, but I’m not persuaded one way or the other.

- Stephen S. Grubbs, MD
Managing partner of Medical Oncology Hematology Consultants
Christiana Care Helen F. Graham Cancer Center, Newark, DE

Disclosure: Dr. Grubbs reported no relevant financial disclosures.

Follow HemOncToday.com on Twitter.