Adjuvant Therapy Phase 3 Trial With RENCAREX®
in ccRCC Patients Approaching Next Milestone
MUNICH—RENCAREX® (INN: girentuximab) is a chimeric monoclonal antibody that binds specifically to carbonic anhydrase IX (CAIX antigen), which is found overexpressed on 90% of clear cell renal cell carcinoma (RCC) cells but is largely absent from normal tissue. Girentuxi-mab also binds to cells of the immune system and activates antibody-dependent cellular cytotoxicity (ADCC), a proven mechanism of action. In several phase 2 studies with girentuximab in metastatic ccRCC, clinical response (defined as objective response or stable disease lasting at least 6 months) was seen in up to 42% of patients.

Subsequently, a large phase 3 trial (the ARISER study) was initiated to examine the efficacy of girentuximab in non–metastatic ccRCC in the adjuvant setting. To be eligible for enrollment, patients had to have been completely or partially nephrectomized and have no detectable metastases, while being at high risk of relapse. During the 6-month treatment phase, patients received weekly injections of girentuximab and were followed closely at regular intervals with CTs, and clinical and safety assessments.

Recruitment exceeded expectations in this multicenter international trial that enrolled a total of 864 patients (planned 854) of which 479 patients are still in long-term follow-up for disease-free survival (DFS) with regular CT scans and for overall survival (OS).

A total of roughly 20,000 doses of girentuximab were administered through February 2009 during the trial with no significant safety issues reported. To date over 35,000 images (predominantly CTs) have been collected for analysis via an independent, central read process.

The trial will have achieved its objective when the DFS of patients in the group treated with girentuximab shows a statistically significant improvement compared to the placebo group. The next relevant milestone is the occurrence of the 343rd relapse. The time for patients to relapse is taking longer than expected. As of the end of March, a total of 317 relapses were reported to WILEX by the local trial centers. The data from all 864 patients will be analyzed once this milestone is reached. Subsequently, an independent interim analysis of the efficacy of girentuximab will be initiated. While the data remain blinded for WILEX, they will nonetheless provide critical information regarding the endpoint of the trial–DFS and could be the basis for filing for approval in the European Union. To date neither the FDA nor the EMEA have approved any drug for the adjuvant therapy of clear cell RRC.

Elevated Blood Pressure May Be Associated With Improved
Clinical Outcomes in Patients Treated with Sunitinib
SAN FRANCISCO – Findings from a retrospective, explora-tory analysis of prospective clinical trials indicate that treatment-related hypertension is associated with significantly greater progression-free survival and overall survival in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib (Sutent®). These data were presented at the 2010 American Society of Clinical Oncology Genitourinary Cancers Symposium.
“The data suggest hypertension associated with Sutent treatment can be a biomarker for antitumor efficacy in these patients,” said Brian Rini, MD, of Cleveland Clinic’s Taussig Cancer Institute in Cleveland, Ohio. “Hypertension, which can be managed, is commonly associated with VEGF inhibitors, and this study is an important contributor to the growing body of knowledge about how best to treat advanced RCC.”Additional research is needed to better understand the underlying biological mechanisms leading to hypertension in order to improve the care of patients who develop hypertension on sunitinib therapy.

Nearly 58,000 people in the United States were expected to be diagnosed in 2009 and nearly 13,000 people were expected to have died from the disease.

Study Results
In this analysis, hypertension was defined (in separate analyses) by maximum systolic blood pressure (SBP) greater than or equal to 140 mmHg or by maximum diastolic blood pressure (DBP) greater than or equal to 90 mmHg. Progression-free survival (PFS) in patients with
a maximum SBP greater than or equal to 140 mmHg (n = 441) was 12.5 months compared with 2.5 months in patients with a SBP less than 140 mmHg (P < .0001). In this same patient population, overall survival (OS) was 30.9 months compared with 7.2 months, respectively (P < 0.0001).

In addition, PFS in patients with a maximum DBP greater than or equal to 90 mmHg (n = 362) was 13.4 months compared with 5.3 months in patients with a DBP less than 90 mmHg (P < .0001). In this same patient population, OS was 32.2 months compared with 14.9, respectively (P < .0001). The incidence of hypertension-associated adverse events was low and similar between patients with and without hypertension. Patients with hypertension experienced slightly more renal adverse events (5% any grade; 2% Grade 3/4) than patients without hypertension (3% any grade; 1% Grade 3/4), which were generally tolerable and manageable.

Epidemiological Update on RCC From the NCI
BETHESDA, MD—An estimated 57,760 men and women (35,430 men and 22,330 women) were diagnosed with and 12,980 men and women were expected to die of cancer of the kidney and renal pelvis in 2009.1

The following information is based on NCI’s SEER Cancer Statistics Review.2

Incidence and Mortality
SEER Incidence
From 2002-2006, the median age at diagnosis for cancer
of the kidney and renal pelvis was 64 years of age3. Approximately 1.3% were diagnosed in persons aged 20 or younger; 1.5% were diagnosed in persons aged 20 through 34; 6.1% were diagnosed in persons aged 35 through 44; 16.4% were diagnosed in persons aged 45 through 54; 24.6% were diagnosed in persons aged 55 through 64; 24.3% were diagnosed in persons aged 65 through 74; 20.0% were diagnosed in persons aged 75 through 84; and 5.7% were diagnosed in persons 85 or older.

The age-adjusted incidence rate was 13.6 per 100,000 men and women per year. These rates are based on cases diagnosed in 2002-2006 from 17 SEER geographic areas.
US Mortality
From 2002 to 2006, the median age at death for cancer of the kidney and renal pelvis was 71 years of age.4 Approxi-mately 0.5% died under age 20; 0.5% between 20 and 34; 2.4% between 35 and 44; 10.2% between 45 and 54; 20.0% between 55 and 64; 25.4% between 65 and 74; 27.9% between 75 and 84; and 13.2% 85+ years of age.

The age-adjusted death rate was 4.1 per 100,000 men and women per year. These rates are based on patients who died in 2002-2006 in the United States.

Survival and Stage
The survival rates presented here are based on the relative survival rate, which measures the survival of cancer patients in comparison with the general population to estimate the effect of cancer. The overall 5-year relative survival rate for 1999-2005 from 17 SEER geographic areas was 68.4%. Five-year relative survival rates by race and sex were: 68.1% for white men; 69.1% for white women; 64.7% for black men; and 67.4% for black women.

The stage distribution shows that 58% of kidney and renal pelvis cancer cases are diagnosed while the cancer is still confined to the primary site (localized stage); 18% are diagnosed after the cancer has spread to regional lymph nodes or directly beyond the primary site; 19% are diagnosed after the cancer has already metastasized (distant stage); for the remaining 4% the staging information was unknown. The corresponding 5-year relative survival rates were: 90.4% for localized; 62.3% for regional; 10.4% for distant; and 37.5% for unstaged.

Lifetime Risk
Based on rates from 2004-2006, 1.43% of men and women born today will be diagnosed with cancer of the kidney and renal pelvis at some time during their lifetime. This number can also be expressed as 1 in 70 men and women will be diagnosed with cancer of the kidney and renal pelvis during their lifetime. These statistics are called the lifetime risk of developing cancer. Sometimes it is more useful to look at the probability of developing cancer of the kidney and renal pelvis between 2 age groups. For example, 0.86% of men will develop cancer of the kidney and renal pelvis between their 50th and 70th birthdays compared with 0.44% for women. (continued >>>)