The American Society of Clinical Oncology (ASCO) has issued recommendations for a preliminary version for a new design for clinical trials during an annual session (June 2, 2013). Recent advancements in science, technologies and therapies have made it necessary for upgrades.
According to Dr. Lee Ellis (committee chair and director of the colorectal cancer translational research program) at the University of Texas M.D. Anderson Cancer Center in Houston, “First, we owe it to our patients to do better”. Secondly, “tumors can be defined by their molecular drivers and we have a better understanding of cancer biology. Immune therapy is working, and we need to exploit this and look for biomarkers.” Thirdly, with limited funding due to economic restraints from funding agencies the question becomes do we run a few large trials or many small ones. If we run small trials, they will have to be done smarter so clinical trial designs need to be reevaluated.
As Dr. Ellis points out, ASCO continues to receive information from the medical community, so these new guidelines are only draft recommendations. The important thing is to “raise the bar” and make better use of genomic medicine to improve clinical outcomes. Ellis also points out that these new guidelines will not go over well with everyone. However, valid arguments will help to build better designs.
For Pancreatic Cancer
Goals: Clinical trials should improve overall survival by 50 percent and that quality of life and toxicity specific to pancreatic cancer be considered.
Two states of pancreatic cancer were considered including metastatic cancer and locally advanced with two treatments including Folfironox (irinotecan, oxaliplatin, leucovorin, and 5-fluorouracil) and gemcitabine. The committee suggests that in the Folfironox group, a meaningful survival would be 4 to 5 months and for gemcitabine, 3 to 4 months.
For Lung Cancer
Goals: Clinical trials should improve overall survival by 25 to 30 percent, minimal increase in toxicity.
For squamous cell disease, the benefit would be an increase of 2.5 to 3 months (HR, 0.77 – 0.80); for nonsquamous cell, it would be 3.25 to 4 months (HR, 0.76 – 0.80).
Two subpopulations were reviewed in the advanced metastatic (stage IV) nonsmall-cell lung cancer group which includes those with squamous cell disease and those with non-squamous. Due to some success with EGFR and ALK mutations, these patients were excluded.
For Breast Cancer
Goals: Cytotoxic therapies provide short benefit (2 to 3 months). A meaningful benefit would be an overall survival of 4.5 months.
Metastatic triple-negative breast cancer previously untreated for metastatic was selected. This group has poor survival due to an absence of validated targeted therapies.
For Colorectal Cancer
Goals: Improve overall survival by 50 percent meaning overall survival somewhere between 3 to 5 months, increase in toxicity minimal. This standard is set for patients who have progressed on standard treatments.
This focuses on patients who have had success on first- or second-line therapy or those who are not candidates for standard therapies. Those with BRAF mutations were excluded from this group.
Future Draft Additions
According to Dr. Ellis, progression-free survival needs to be recorded and 1- to 2-year survival recommendations need to be reviewed. The number of patients acceptable (sample size) for a given clinical trial needs to be established to provide for meaningful clinical outcomes.