Advances in Colorectal Cancer - Episode 8
For High-Definition, Click
Accurately measuring clinical progression in patients with metastatic colorectal cancer (mCRC) has become increasingly more challenging as treatment approaches continue to improve. As a result, treatment decisions should be based on clinically meaningful parameters, since progression varies based on the effectiveness of the treatment, explains Heinz-Josef Lenz, MD. Stressing this point further, both Lenz and Claus-Henning Köhne, MD, PhD, believe it is important to base treatment decisions on patient parameters and not strictly on CEA results.
In addition to practice implications, the dimensions used to measure progression affect sequencing therapies and clinical trials. Looking more closely at clinical trials, Axel Grothey, MD, reviews findings from the phase III CORRECT trial that examined the multikinase inhibitor regorafenib. This trial enrolled patients with mCRC who had progressed on all standard components of therapy.
An interesting parameter of the CORRECT trial, Grothey notes, was the use of a placebo without crossover. To ease concerns with this design, the trial randomized patients 2:1 to receive regorafenib or placebo plus best supportive care. Initially, Grothey notes, researchers expected it to be difficult to enroll the required 690 patients in 26 months; however, the trial quickly enrolled 760 patients in only 10 months. The speed of enrollment to this trial was a clear sign of an unmet medical need, Grothey believes.
For the primary endpoint of overall survival, the trial was positive with a hazard ratio of 0.77, showing a 23% reduction in the risk of death, Grothey explains. Trends in this data have prompted researchers to look for a potential biomarker of response; however, this investigation is still ongoing. Overall, Grothey adds, regorafenib did not show an impact on response rates but did show a clear benefit for delaying tumor progression, which is expected in the last-line setting.
Side effects with regorafenib were similar to other multkinase inhibitors, which include skin reactions, diarrhea, fatigue, and anorexia. As a result of these side effects there is a need to further refine the usage of this agent, Köhne believes, especially as the drug is moved into earlier lines of therapy. Along these lines, Köhne and other panelists, question whether the correct dose has been discovered. When evaluating the benefits of this trial, Lenz stresses the importance of utilizing hazard ratios, since median numbers do not always capture the full benefit of a drug.