ASCO 2007: Steady Progress Against Cancer
On June 1-5, Chicago played host to this year's American Society of Clinical Oncology (ASCO) meeting. This year set an attendance record with more than 30,000 participants. Throughout the meeting one sensed the excitement of steady, continued progress. There was also anticipation of even greater changes that will occur in the coming years as laboratory science is enabled by new and rapidly evolving technology. The anticipation was clearly about earlier diagnosis, new and reliable biomarkers, highly characterized tumors, and more targeted therapies.
For example, as the lead story in this issue of the NCI Cancer Bulletin discusses in greater detail, a phase III European clinical trial found that, compared with placebo, the multitargeted agent sorafenib (Nexavar) improves survival in advanced hepatocellular carcinoma (HCC). There was a small, but statistically significant, improvement, marking the first time a systemic treatment has proven effective against advanced HCC, a notoriously intractable disease that is increasing in incidence in the U.S. The result clearly sets the stage for further trials testing sorafenib in combination with other targeted agents to treat HCC.
Also impressive was a larger, phase III clinical trial that showed a significant treatment benefit against another difficult to treat disease, small-cell lung cancer (SCLC). Using prophylactic cranial irradiation, or PCI, in patients with extensive SCLC who had responded to chemotherapy, not only was the risk of symptomatic brain metastases reduced compared to those not receiving PCI, but there was a highly significant survival improvement at one year. There seemed to be consensus at the meeting that this finding should immediately change clinical practice.
After demonstrating particularly powerful prognostic prowess in metastatic breast cancer, new data presented at ASCO suggested that levels of circulating tumor cells (CTCs) - tumor cells circulating freely in blood - in men with metastatic, hormone-refractory prostate cancer are predictive of prognosis and response to chemotherapy. This new study also suggests CTC levels may be a better surrogate of treatment efficacy than PSA levels.
During the meeting, preliminary data were presented from the first prospective, multicenter phase II clinical trial in the U.S. testing gefitinib (Iressa) as a first-line therapy in patients with advanced non-small-cell lung cancer with genetic mutations known to correspond with gefitinib response. The initial findings demonstrated strong progression-free survival, and the estimated median overall survival of approximately 21 months would be a significant improvement compared with historical rates. The trial, called iTARGET, represents an important step toward more individualized treatment.
Finally, it is important to touch on the results of a small, but entirely new type of clinical trial being pioneered at NCI that we believe will ensure promising agents get translated to the clinic more quickly and efficiently than in the past. Following new FDA guidance released last year - and developed with the aid of the FDA-NCI Interagency Oncology Task Force - this "early phase I trial" involved only six patients. It tested an inhibitor of an enzyme called PARP that plays a critical role in DNA repair. Assays developed as part of the trial showed that the agent, ABT-888, was hitting its intended target in tumor cells, as well as in white blood cells, suggesting that future early-phase trials of the drug can use white blood cells as biomarkers of the compound's effectiveness.
Just before the ASCO meeting began, NCI's Scientific Director for Clinical Research, Dr. Lee Helman, participated in a meeting with the Sarcoma Alliance for Research through Collaborations to review the findings from phase I clinical trials testing investigational monoclonal antibodies that inhibit IGF-1R, including some extremely promising results seen in patients with Ewing's sarcoma, a cancer rare in adults but common in children. In some cases, there have been complete responses in patients with refractory, progressive disease who had failed multiple therapies. Based on these results, several phase II studies have been planned, at least one of which is scheduled to launch in the fall. I am very hopeful that positive results of these trials may be presented at future ASCO meetings.
This year's ASCO meeting demonstrated the important progress being made against different cancer types through varied approaches. It demonstrates how we are learning to design better trials and take advantage of new technologies. Most important, it confirms that we are improving outcomes for more and more people who receive a cancer diagnosis.
Dr. John E. Niederhuber