In a phase III trial reported in The Lancet Oncology, Tamas Hickish, MD, of Poole Hospital NHS Foundation Trust, Dorset, England, and colleagues found that treatment with MABp1, an antibody that targets interleukin 1α and exhibits antitumor activity, was associated with improvement in the composite outcome of stabilizing/improving lean body mass and debilitating symptoms in patients with advanced colorectal cancer.
In the double-blind trial, 333 patients from 42 outpatient clinics in Europe and Russia were randomized 2:1 between May 2014 and September 2015 to receive intravenous MABp1 at 7.5 mg/kg or placebo every 2 weeks for 8 weeks. Patients had metastatic or unresectable disease, an Eastern Cooperative Oncology Group performance status of 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis. Their disease was refractory to oxaliplatin and irinotecan.
The primary endpoint was a composite of stable or increased lean body mass on DEXA (dual-energy x-ray absorptiometry) and stability or improvement in at least two of the three symptoms of fatigue, pain, and anorexia on the European Organisation for Research and Treatment of Cancer Quality of Life in Cancer questionnaire (EORTC QLQ-C30) at week 8 compared with baseline. Outcome was assessed in patients who received at least one dose of MABp1 (n = 207) or placebo (n = 102). After the 8-week double-blind phase of the study, all patients from either group could receive MABp1 in an open-label extension phase.
Outcomes
Overall, the primary endpoint was achieved in 33% of patients in the MABp1 group vs 19% of patients in the placebo group (relative risk = 1.76, P = .0045). In a post hoc analysis by component, sustained or improved lean body mass occurred in 51% vs 45% (P = .18), and sustained or improved symptoms occurred in 45% vs 44% for pain (P = .45), 45% vs 45% for fatigue (P = .48), and 55% vs 48% for anorexia (P = .12).
After 8 weeks of treatment, 17% vs 12% of patients had stable disease (hazard ratio [HR] for disease progression = 1.26, P = .14). Overall survival data were available for 116 patients in the MABp1 group and 59 patients in the placebo group; of the placebo group, 36 patients (61%) received MABp1 in the open-label extension.
In an exploratory analysis, median overall survival was 6.1 months in the MABp1 patients vs 2.4 months in the 23 placebo patients who received only placebo (P = .0002). Among the MABp1 patients, median overall survival was 11.5 months vs 4.2 months in those achieving vs not achieving the primary endpoint (P < .0001).
Adverse Events
The most common grade 3 or 4 adverse events in the MABp1 group were anemia (4% vs 5% of placebo group), increased alkaline phosphatase (4% vs 2%), fatigue (3% vs 7%), and increased aspartate transaminase (3% vs 2%). Serious adverse events occurred in 23% vs 32% (P = .07). After 8 weeks, 8% of patients in the MABp1 group and 11% of patients in the placebo group had died, with none of the deaths considered related to treatment.
The investigators concluded: “The primary endpoint was a useful means of measuring clinical performance in patients. MABp1 might represent a new standard in the management of advanced colorectal cancer.”
The study was funded by Biotech. ■
