A novel anti–interleukin-1 alpha (IL-1α) antibody has shown a significant impact on symptoms and a high level of safety and tolerability in patients with advanced colorectal cancer, according to phase III data presented by Hickish et al at the European Society for Medical Oncology’s 18th World Congress on Gastrointestinal Cancer in Barcelona.1 MABp1 is the first monoclonal antibody immunotherapy to specifically target and neutralize IL-1α, one of the most potent inflammatory substances manufactured by the body or tumor cells.
Tamas Hickish, MD
“IL-1α in tumors promotes angiogenesis, helping to provide crucial blood supply for tumor growth, and it can also send the body’s metabolism out of control, causing it to burn muscle and lose weight,” said lead investigator Tamas Hickish, MD, of the Royal Bournemouth Hospital. At the same time, IL-1α’s neurologic effects can contribute to the fatigue, anxiety, and anorexia associated with advanced cancer.
The study enrolled 309 patients with metastatic colorectal cancer whose disease had not responded to standard chemotherapy with oxaliplatin and irinotecan and who showed a high degree of symptoms, functional impairment, weight loss, or elevated systemic inflammation. IPatients were randomized them in a 2:1 ratio to receive MABp1 with best supportive care or placebo and the same. In addition to evaluating the new agent, researchers also implemented new criteria for objective response based on control of symptoms, which were developed in collaboration with the European Medicines Agency’ Scientific Advice Working Group. These criteria were applied in conjunction with dual-energy x-ray absorptiometry and EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 to assess disease control.
Treatment with MABp1 was associated with a significant 76% relative increase in clinical response rate. Patients who showed a clinical response lived almost three times as long as those who did not respond (11.5 months vs 4.2 months).
Researchers also found that measures of improved health status correlated with improvement in almost all other self-reported and laboratory-based measures of health, including with improved control of tumor-related white blood cell activity and reduced systemic inflammation.
There were also one-quarter fewer serious adverse events in the treatment arm of the study compared with the placebo arm.
“These data suggest [MABp1] is very well tolerated and has the potential to meet the real and urgent need for more effective, less toxic therapies for patients with advanced colorectal cancer,” Dr. Hickish said. “This study also provides the first evidence that health status can actually be used to measure efficacy of antitumor therapy in advanced, refractory colorectal cancer and that clinical responses based on health status can be a predictor of overall survival benefit.” ■