Pfizer Inc. announced data from the pivotal phase 3 AXIS 1032 trial, showing that in patients with previously treated advanced renal cell carcinoma (RCC), axitinib significantly extended progression-free survival (PFS) [HR=0.665, 95% CI; P<0.0001], with a median PFS of 6.7 months (95%CI, 6.3-8.6), compared with 4.7 months (4.6-5.6) for those treated with sorafenib, a standard of care for this patient population. PFS was significantly longer in axitinib-treated patients compared to those treated with sorafenib, regardless of prior therapy with Sutent (sunitinib malate) or cytokines. These data will be presented on June 6th at the 47th Annual American Society of Clinical Oncology (ASCO) meeting in Chicago from June 3-7, 2011.

“We are very pleased that this phase 3 trial met its primary endpoint and demonstrated that axitinib could prolong median PFS to more than six months in patients with previously treated advanced RCC. It is notable that in the subset of patients previously treated with cytokines, axitinib extended median PFS to greater than a year," said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit. “We hope that axitinib will be approved as an additional therapeutic option for patients with advanced RCC, alongside Pfizer’s two medications approved in this disease, Sutent and Torisel.”

Pfizer is working with global health authorities on filing submissions for axitinib in RCC.

In this global study, including centres in the US, EU and Japan, 723 patients with clear-cell advanced RCC who had progressed following prior therapy with regimens containing sunitinib (54 per cent), cytokines (35 per cent), bevacizumab (8 per cent) or temsirolimus (3 per cent) were enrolled. Participants received either axitinib at a starting dose of 5mg twice daily or sorafenib 400mg twice daily (N=361 and 362). PFS was statistically significantly longer in axitinib-treated patients in both the prior cytokine-treated subgroup (12.1 vs 6.5 months; P<0.0001) and the prior sunitinib-treated subgroup (4.8 vs 3.4 months; P=0.0107), with a 43 per cent improvement in median PFS in the overall patient population, compared to sorafenib. In a secondary endpoint, objective response rates (either complete or partial responses assessed by independent central review) were more than doubled with axitinib compared to sorafenib in the overall patient population (19.4 per cent vs 9.4 percent, P=0.0001). (Abstract #4503)

Consistent with previous analyses, axitinib demonstrated a generally manageable safety profile in this study. The study abstract lists the following common adverse events (all grade), which occurred more frequently in the axitinib arm compared to sorafenib: hypertension (40 per cent), fatigue (39 per cent), dysphonia (31 per cent), and hypothyroidism (19 percent).

In an additional oral abstract evaluating patient-reported outcomes (PRO), a secondary endpoint of the AXIS study, patients treated with axitinib reported similar kidney cancer-specific quality of life scores compared to patients treated with sorafenib, and a delay in a pre-specified composite endpoint, which consisted of death, disease progression and worsening of quality of life. (Abstract #4504)

“These data, from the first head-to-head phase 3 study comparing active targeted therapies in advanced RCC, are important for clinicians as they help us advance our understanding of this tumour, where there are limited proven options for previously-treated patients,” said Dr. Brian I. Rini, Taussig Cancer Institute at Cleveland Clinic, who served as principal investigator of this Pfizer-sponsored study and has been a paid consultant to Pfizer Oncology. “The clinically meaningful improvement in PFS seen with axitinib is even more encouraging as it was accompanied by generally manageable tolerability, an important consideration for these patients.”

Each year, approximately 210,000 people worldwide are diagnosed with kidney cancer and nearly 102,000 people are expected to die from the disease. Within the last five years, great advances have been made in the treatment of patients with advanced RCC, the most prevalent form of kidney cancer. However, five-year survival rates for patients with advanced RCC remain low, at around 20 per cent.

Axitinib is an oral and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, receptors that can influence tumour growth, vascular angiogenesis and progression of cancer (the spread of tumours). Axitinib is an investigational agent that has not been approved by regulatory agencies.

Axitinib is also being investigated in a randomized phase 3 clinical trial in patients with treatment-naïve as well as previously treated advanced RCC, and in a randomized Phase 2 clinical trial for the treatment of hepatocellular carcinoma (HCC).

As a leader in the treatment of advanced RCC, Pfizer Oncology is dedicated to offering multiple treatments and investigating new agents in different populations and stages of disease. Pfizer’s RCC portfolio offers two approved therapies for the treatment of people with advanced RCC, Sutent (sunitinib malate) and Torisel (temsirolimus). By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, licensing partners and people affected, we are committed to advancing the science of RCC through research into established and novel compounds, as well as the exploration of biomarkers to better personalize therapy.

SUTENT is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important SUTENT targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are expressed by many types of solid tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT also inhibits other targets important to tumour growth, including KIT, FLT3 and RET.

Torisel is the only intravenous mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma (RCC).

Based on preclinical studies, Torisel inhibits the activity of mTOR, an intracellular protein implicated in multiple growth-related cellular functions including proliferation, growth and survival. The inhibition of mTOR also reduces levels of certain growth factors, such as vascular endothelial growth factor (VEGF), which are overexpressed in solid tumors like kidney cancer and are thought to play a crucial role in angiogenesis, the process by which tumours acquire blood vessels, nutrients and oxygen needed for growth.

Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide.