ASCO: Evolving Targeted Therapies in Lung Cancer

CHICAGO, June 5 -- The success of targeted therapies in lung cancer depends not only on identifying the correct molecular target but also on targeting patients who are likely responders, oncologists here said.

"We need to develop tools to find good responders," said Roman Perez-Soler, M.D., of Albert Einstein College of Medicine in New York.

"Just a few years ago we would have been unable to fill 15 minutes on this topic, now we are giving it an entire presentation," he said at an industry-sponsored satellite symposium held in conjunction with the American Society of Clinical Oncology meeting.

However, symposium chairman Giuseppe Giaccone, M.D., Ph.D., of the National Cancer Institute in Bethesda, Md., suggested that "It is unlikely that we will find that answer-a patient selection paradigm-soon."

Dr. Perez-Soler spoke of the need to individualize therapies in non-small cell lung cancers based on both tumor biology and varying patient characteristics.

For example, commented Fred Hirsch, M.D., Ph.D., of the University of Colorado Cancer Center in Aurora, Colo., certain mutations in the epidermal growth factor receptor were specifically sensitive to erlotinib (Tarceva).

"These mutations present more frequently in women -- independent of smoking -- in cases of adenocarcinoma, and in Asian patients who were born in Asia," Dr. Hirsch explained.

In a study of erlotinib versus placebo, almost 25% of patients who had never smoked responded to erlotinib therapy versus a 9% response in current and former smokers, said Pasi Jnne, M.D., Ph.D., of the Dana-Farber Cancer Institute and Harvard.

He suggested that erlotinib and another epidermal growth factor receptor inhibitor, gefitinib (Iressa), might be used together in treating lung cancer in those selected patients who had never smoked cigarettes.

Epidermal growth factor receptors turn medical oncologists into pseudo-dermatologists, said Corey Langer, M.D., of Temple University in Philadelphia.

The first sign of erlotinib response, he explained, is often a characteristic acne-like rash on a patient's trunk and face. "We have to learn how to prescribe different drugs to treat these rashes," he said.

Dr. Langer described the delicate balancing act of toxicity, quality of life, and efficacy in the treatment of non-small cell lung cancer in the era of targeted therapies.

Alan Sandler, M.D., of Vanderbilt University, discussed the key E4599 study of the Eastern Cooperative Oncology Group in which the vascular endothelial growth factor inhibitor bevacizumab (Avastin) was added to standard therapy of carboplatin and paclitaxel in lung cancer.

"In this trial the combination of the targeted agent with the chemotherapy agents worked better than the chemotherapy drugs alone," he said.

The patients taking bevacizumab plus carboplatin and paclitaxel achieved a 12.5-month survival compared to 10.2 months for treatment without bevacizumab-a statistically significant difference (P=0.0075), Dr. Sandler said.

Dr. Giaccone noted that cancer vaccines also hold promise as targeted-treatment. He said that of the vaccines in clinical development, some studies have shown survival rates of as long as 18 months (Allogenic Ad B 7.1).

Dr. Hirsch disclosed possible financial conflicts of interest with Genentech BioOncology, OSI Pharmaceuticals and Lilly Oncology. Dr. Perez-Solar disclosed financial conflicts of interest with Amgen, AstraZeneca, Genentech BioOncology, Lilly Oncology, Novartis Oncology, and Transave. Dr. Sandler disclosed possible financial conflicts with Amgen, AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Cyclocel, Genentech BioOncology, OSI Pharmaceuticals, Lilly Oncology, Pfizer Oncology, Sanofi-Aventis, and Wyeth Pharmaceuticals.

Dr. Langer disclosed possible financial conflicts of interest with Genentech BioOncology and OSI Pharmaceuticals. Dr. Jnne disclosed possible financial conflicts of interest with Genentech BioOncology and Genzyme. Dr. Giaccone had no relevant financial relationships to disclose.