Director's Update: June 15, 2004

Charting Our Progress: Targeted Therapies Coming into Their Own

The words "targeted therapy" were on everybody's lips last week at the 40th annual ASCO meeting. And with good reason. Encouraging results were reported in a number of clinical trials, proving that we are making progress in our efforts to attack cancer at its most fundamental levels.

In one phase III trial, for example, use of the investigational agent erlotinib (Tarceva) - which, like the recently FDA-approved gefitinib (Iressa), targets the epidermal growth factor receptor - improved survival in patients with advanced lung cancer. In another phase III trial, bortezomib (Velcade), which inhibits the proteasome pathway and affects both cancer cell proliferation and stability, significantly improved 1-year survival in multiple myeloma patients who had relapsed or become resistant to standard therapies. And several earlier stage trials involving the investigational anti-angiogenesis drugs SU11248 and BAY 43-9006, both of which are multitargeted agents, also demonstrated promise in treating metastatic renal cell carcinoma.

Other studies shed light on additional avenues of treatment, such as combining new therapies. One intriguing combination therapy that had positive results in metastatic renal cell carcinoma was the use of erlotinib and the vascular endothelial growth factor inhibitor bevacizumab (Avastin), which was recently approved by the FDA.

Studies presented at ASCO also showed that we are learning to use existing therapies more effectively. As you may have read in last week's Bulletin, for instance, adjuvant chemotherapy after surgery for lung cancer had striking results, effectively creating a new standard of care for patients with advanced lung cancer. Or, as reported in this issue, in a study of patients with metastatic breast cancer, weekly administration of paclitaxel proved superior to the more conventional approach of administration every 3 weeks.

Of course, not all of the data presented at this year's meeting were positive; nor should we expect them to be. We are engaged in a difficult scientific pursuit to outwit and outmaneuver a stealthy and adaptable foe that has shown an uncanny ability to return after we thought and hoped it was long gone.

More important, though, the results from this year's ASCO meeting demonstrate that we are on the right course. Discussions of "targeted therapies" in years past were often shrouded in tones of uncertainty. Just a few years later, these therapies represent a major theme of perhaps the most important clinical oncology meeting in the world. Meanwhile, we are using advances in areas like genomics to learn how we might use these therapies more effectively. Several recent studies have found, for example, genetic mutations that were predictive of a positive response to targeted therapies, while others have discovered "genetic signatures" that may help predict response to treatment.

The excitement was palpable among the presenters and their audiences during the ASCO presentations. There was cautious optimism that we are moving closer to providing better, less toxic treatments that will aid in curing some cancers while allowing us to manage others like a chronic disease.

Yes, at times there has been uncertainty. At other times, there have been hopeful discussions about the day when we might be able to apply advances like those presented at ASCO in the everyday treatment of our patients. And now, we are on the brink of translating that hope into reality.

Dr. Andrew C. von Eschenbach
Director, National Cancer Institute