Biomarker Identified in Relation to Drug Response in Refractory Urothelial Cancer
by AACR Communications Staff
•Pazopanib achieved the primary endpoint of response.
•Interleukin-8 may be an indicator of tumor resistance and poor survival.
•Data need further validation in a large patient population.
CHICAGO — The antiangiogenic drug pazopanib has demonstrated clinically meaningful activity in patients with refractory urothelial cancer, according to results presented at the AACR Annual Meeting 2012, held here March 31 – April 4. The results also revealed that increases in interleukin-8 levels early after treatment with pazopanib may predict a lack of tumor response to the therapy.
"Historically, prognosis of patients with relapsed or refractory urothelial cancer is quite dismal," said Andrea Necchi, M.D., faculty member in the department of medicine at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. "Patients who fail to be cured after multiple chemotherapy regimens have a poor survival estimate, and palliative care is a reasonable trade-off."
Data from the phase II proof-of-concept trial identified pazopanib as the first targeted compound to have clinically meaningful activity in patients with refractory urothelial cancer, according to Necchi.
"Our data indicate that pazopanib seems to be a legitimate drug in this disease," said Necchi. "Most interestingly, our biomarker analysis clearly pointed out the role of rising levels of circulating interleukin-8 as an early and potentially practice-changing indicator of tumor resistance and poor survival."
The researchers assigned 41 patients with relapsing or progressing urothelial cancer between 2010 and 2011 to 800 mg once-daily pazopanib. All patients had at least one prior chemotherapy regimen for metastatic disease.
At follow-up, seven patients had a partial response to therapy and 24 patients had stable disease — an overall clinical benefit of 76 percent. Median progression-free survival was 2.6 months, and median overall survival was 4.7 months. However, 10 percent of patients had a long-term cure after a median follow-up of 19 months.
The researchers examined blood samples for predictive biomarkers at baseline and every four weeks. They found that early rising levels of interleukin-8 (e.g., after four weeks of pazopanib) were associated with tumor progression and shorter overall survival.
"This trial gave a clear proof of concept that will require confirmation on a larger number of patients," Necchi said. "However, the preliminary findings, mainly regarding the role of interleukin-8 levels, have the potential to change at least the concept of new trial design with antiangiogenic agents in this disease."
Necchi served as an adviser and consultant for GlaxoSmithKline Inc. The current study was sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori. GlaxoSmithKline Inc. provided the drug supply and granted independent radiologic review, which was performed at Columbia University Medical Center.
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Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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