Phase 2 Study Shows Benefit of Erlotinib in Invasive Bladder Cancer

Kathleen Louden

October 16, 2009

October 16, 2009 (Chicago, Illinois) — Muscle-invasive bladder cancer improved in 75% of patients who received targeted therapy with erlotinib (Tarceva) before undergoing radical cystectomy, a new pilot study has found. In addition, only 30% of the patients died of the disease within 2 years of treatment, suggesting that erlotinib prolongs disease-specific survival for people with bladder cancer, the authors say.

"Typically, 50% of patients will be alive at 2 years," said lead author Angela Smith, MD, a surgical resident in the Urologic Surgery Division at the University of North Carolina at Chapel Hill (UNC). "These preliminary results are encouraging."

Dr. Smith presented the results here at the American College of Surgeons 94th Annual Clinical Congress, and she and a coauthor spoke to Medscape General Surgery during a press conference.

First Use of Erlotinib in Nonmetastatic Bladder Cancer

"This is the first clinical application using a targeted agent in [treating] localized bladder cancer," said coauthor Raj Pruthi, MD, associate professor of surgery and urology at UNC.

The new study enrolled 20 patients (15 men) with histologically confirmed muscle-invasive bladder carcinoma (clinical stage T2) after they underwent initial transurethral resection of bladder tumor. All patients received neoadjuvant therapy with 150 mg daily of erlotinib orally for 4 weeks before a radical cystectomy. Erlotinib, an inhibitor of epidermal growth-factor receptor, is approved by the US Food and Drug Administration for the treatment of nonsmall-cell lung cancer and pancreatic cancer.

On surgical pathological specimens, there was either no evidence of disease or it was now confined to the bladder (less than or equal to pT2) in 15 patients, the authors reported. Of the remaining 5 patients, 4 had cancer invading perivesical fat (pT3) and 1 patient had a single positive lymph node (pT0N1), Dr. Pruthi told Medscape General Surgery.

Four patients with organ-confined disease subsequently had disease progression and received cytotoxic chemotherapy, as did the patients who did not initially respond to erlotinib, the authors said. All but 3 of the 20 patients continued erlotinib maintenance therapy postoperatively. At a mean follow-up of 25 months, 9 patients had died — 6 from the cancer and 3 from other causes, Dr. Pruthi said.

Adverse Effects Tolerable, Drug Cost a Problem

Adverse effects of erlotinib were tolerable, with the most common being a rash, the authors said. Twelve of the 15 patients who experienced a rash had organ-confined disease, according to Dr. Smith, who said that "there seems to be a correlation between response to the drug and development of the rash."

The authors plan to study larger numbers of patients. "It is too early to offer a definitive conclusion," she said.

Although the study was very small, these preliminary data are "intriguing" and merit further study, James Montie, MD, professor of urologic oncology at the University of Michigan in Ann Arbor, told Medscape General Surgery. Dr. Montie, who was not affiliated with the study, said: "Whether erlotinib is going to be better than what we have now is unclear."

He added that the high cost of erlotinib could be a drawback to future expanded use of erlotinib.

OSI Pharmaceuticals, maker of Tarceva, provided the drug and partial funding for the study. Dr. Montie has disclosed no relevant financial relationships.

American College of Surgeons (ACS) 94th Annual Clinical Congress. Presented October 13, 2009.

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