By Laurence H. Baker, DO
Chair, Southwest Oncology Group
Laurence H. Baker, DO, is the Chair of the Southwest Oncology Group (SWOG). Leading this cooperative group since 2005, Dr. Baker is dedicated to clinical investigations of innovative treatments for cancer, but also to improving the efficiency and quality of the clinical trial process. In the article that follows, he discusses an actively recruiting phase III trial (S0819) that not only explores the efficacy of treatments for advanced non-small cell lung cancer (NSCLC), but also showcases a new methodology for making clinical investigation more efficient.
Lung cancer takes a devastating toll in the United States. Only 15% of patients with the disease survive five years after their diagnosis. It is the most frequent cause of cancer death in the country, a fact that is largely due to the high numbers of patients who present in the advanced stages of disease when effective therapies are limited. One emerging method that holds promise for improving the grim toll of NSCLC is the use of biomarkers to detect expression of increased copy number of the epidermal growth factor receptor (EGFR) gene, identified through fluorescent in situ hybridization (FISH).
EGFR FISH assays are a part of oncology’s advance into smarter medicine. These biomarkers allow us to identify which patients with NSCLC will benefit the most from a particular drug regimen. Such identification helps eliminate the trial-and-error aspect of chemotherapy and saves valuable time and resources in the lives of these patients.
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Enrolling Patients in SWOG S0819
Title: A randomized, phase II study comparing carboplatin/paclitaxel or carboplatin/paclitaxel/bevacizumab with or without concurrent cetuximab in patients with advanced non-small cell lung cancer (NS CLC).
Endpoints: The primary endpoints of this trial are overall survival of the entire study population and progression-free survival of patients who are EG FR FISH -positive.
Inclusion Criteria: Entry criteria include, but are not limited to, the following:
- Histologically or cytologically confirmed stage IV advanced primary NSCLC
- No prior chemotherapy, cetuximab, gefitinib, erlotinib, or other investigational agents that target the EG FR pathway
- Patients must have recovered from all associated toxicities of radiation therapy at the time of registration
- Zubrod Performance Status of 0-1
Contact Information:
Roy S. Herbst, MD, PhD, Study Coordinator
Phone: 713-792-6363
For more information on S0819, visit www.swog.org. |
In this phase III trial, S0819, patients will begin chemotherapy regimens with carboplatin and paclitaxel with or without bevacizumab, depending on their suitability for that drug. Patients will be randomly assigned to continue that treatment alone or to receive concurrent cetuximab. Although the primary endpoints of the trial will examine the efficacy of these treatments, more importantly, we are critically examining the value of EGFR FISH in determining which patients will derive the greatest benefit from these drugs.
S0819 also represents an important change for SWOG and the general conduct of clinical trials. In 2006, a group led by David Dilts, PhD, of Oregon Health and Science University, reported that the average length of time for a phase III trial to move from initial conception to activation in a cooperative group system was nearly 800 days (J Clin Oncol. 2006:24;4553-7.). This unfortunate number is frequently cited by critics of cooperative groups and cancer centers. Although there has been much discussion of this study, few efforts have been made to try to change the system. This trial represents SWOG ’s first attempt to start making such a change.
We developed a mechanism called SWAT (the Southwest Oncology Group Action Team), a group composed of all of the trial’s key players. Since the trial’s conception in October 2008, all members of the SWAT team convened weekly for a conference call to discuss progress and to move the trial past any unnecessary delays. This kind of vigilance and a little healthy peer pressure made the team members work more efficiently than they normally might have. As a result, the time required from the conception of this trial to its date of accrual is approximately 270 days—nearly one-third of the original length observed by Dr. Dilts. Now that we have evidence that the method works, we plan to implement it in future SWOG trials.
For many reasons, we are very excited about this trial. Not only will it test the potential of a chemotherapy regimen, but it will shed light on the efficacy of a promising biomarker for patients with NS CLC. It also represents a tremendous success in SWOG ’s development of new methods to conduct studies more efficiently. We hope this success will ultimately benefit our patients in their fight against cancer.
