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FDA Approves First New Therapy In a Decade For Most Lethal Cancer

Nov. 2, 2005, 4:14 PM

The U.S. Food and Drug Administration has approved the first new therapy in almost a decade for pancreas cancer, the fourth leading cause of cancer death in the United States.

The FDA approved the addition of the targeted agent erlotinib (marketed as Tarceva) to the chemotherapy drug gemcitabine, which has been the only approved therapy for advanced pancreas cancer since its approval in 1996. The approval of Tarceva was based on a study demonstrating the combination increased overall survival by 23 percent and “progression-free survival” by 30 percent over treatment with gemcitabine alone.

These improvements were both statistically significant and clinically meaningful and were made without sacrificing overall “quality of life” due to side effects, said Mace L. Rothenberg, M.D., Ingram Professor of Cancer Research and director of Phase I Drug Development at the Vanderbilt-Ingram Cancer Center.

“Tarceva plus gemcitabine is an important treatment option for patients and physicians who want a more aggressive, more effective treatment for advanced pancreas treatment,” said Rothenberg, who testified in favor of approval before the FDA’s Oncology Drug Advisory Committee.

The American Cancer Society estimates that 32,180 Americans will be diagnosed with pancreas cancer in 2005, and 31,800 Americans will die of the disease.

Rothenberg spoke from considerable experience, having helped lead the trial that resulted in the approval of gemcitabine for pancreas cancer a decade ago.

Since that time, he noted, no fewer than 10 Phase III trials have been conducted in which a new drug has been combined with or compared to gemcitabine. None prolonged survival. Pancreas cancer has the shortest median survival of any solid tumor. Half of patients with pancreas cancer die within six months of diagnosis, and fewer than 4 percent of patients are living five years after diagnosis.

“Clearly, improvements in outcome for patients with advanced pancreas cancer have been more difficult than we ever anticipated,” Rothenberg said. “Should the combination of Tarceva and gemcitabine be the new standard therapy for advanced pancreas cancer? I would say that it is a welcome option for patients and physicians confronting this difficult diagnosis.”

Tarceva, an oral medication, was initially approved in 2004 for treatment of non-small cell lung cancer. It works by blocking signals from the epidermal growth factor receptor (EGFr) that prompts cell growth.

Over-expression of this receptor is common in pancreas cancer. Increased levels of EGFr are associated with more aggressive disease and a worse prognosis for patients with pancreas cancer, and in preclinical studies, inhibition of EGFr enhanced gemcitabine’s tumor-killing effects.

However, in this study, whether a patient’s tumor overexpressed EGFr did not correlate with response to the Tarceva-gemcitabine combination. Additional research is under way with this and other “targeted agents” to better understand how they work and to better select patients who are likely to respond to them.

The study on which the approval was based was a randomized, double-blinded trial involving 569 patients and was conducted by the National Cancer Institute of Canada Clinical Trials Group. The drug was provided by OSI Pharmaceuticals, for which Rothenberg is a consultant.

In this study, the difference in median survival was only about 12 days. Rothenberg noted that median survival – the point at which half the patients on trial have died – did not convey the overall survival advantage afforded from the addition of Tarceva. Median survival is a “point estimate” that is frequently used to compare arms of clinical trials. “This single point estimate did not capture the true survival benefit seen in this study,” Rothenberg said.

Pancreas cancer remains a particularly challenging tumor to treat because patients tend to be diagnosed after the disease has spread to other organs (metastasized).

“Pancreas cancer tends to metastasize very early, before symptoms occur and when the primary tumor is quite small,” Rothenberg said. “Sometimes we can’t even find the primary tumor even though the patient has presented with metastatic disease.

“That’s why research like that of Lynn Matrisian (chair of Cancer Biology at Vanderbilt) to understand the process of cancer metastasis is critically important. We must figure out what makes this cancer metastasize so early and so aggressively.”

Risk factors for pancreas cancer include cigarette and cigar smoking – the incidence is twice as high among smokers as non-smokers. Risk also appears to increase with obesity, physical inactivity, chronic pancreatitis, diabetes and cirrhosis, according to the American Cancer Society.

Media Contact:
Heather Hall, 615-322-4747
Heather.l.hall@vanderbilt.edu

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