In patients with metastatic or unresectable colorectal cancer refractory to oxaliplatin and irinotecan, treatment with MABp1 was significantly associated with stable or increased lean body mass and stability or improvement in symptoms at 8 weeks compared with placebo, according to a study published in The Lancet Oncology.1
MABp1 (Xilonix) is an interleukin 1α-targeting antibody that has been associated with antitumor activity and relief of debilitating symptoms in patients with advanced colorectal cancer. Therefore, researchers sought to evaluate the impact of MABp1 using a new primary end point in this population.
For the ongoing, double-blind, phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT02138422), investigators enrolled 333 patients with metastatic or unresectable colorectal cancer who were refractory to oxaliplatin and irinotecan. Patients were eligible to participate if they had an Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis.
Participants were randomly assigned 2:1 to receive an intravenous infusion of MABp1 at a dose of 7.5 mg/kg or placebo every 2 weeks for 4 doses. Investigators assessed the novel primary end point, a composite of stable or increased lean body mass and stability or improvement in 2 of 3 symptoms (pain, fatigue, or anorexia) at week 8 compared with baseline measurements, in patients who received at least 1 dose of MABp1 or placebo.
Results showed that 33% of patients who received MABp1 achieved the primary end point compared with 19% of patients given placebo (relative risk, 1.76; 95% CI, 1.12-2.77; P =.0045).
The most frequent reported grade 3 to 4 adverse events in the MABp1 arm were anemia (4%), elevated alkaline phosphatase (4%), fatigue (3%), and increased AST concentration (3%). There was no significant difference in the incidence of serious adverse events between the 2 arms (P =.07).
During follow-up, 8% and 11% of patients in the MABp1 group and the placebo group, respectively, had died; however, no deaths were determined to be related to treatment.
The findings suggest that MABp1 may represent a new standard in the management of patients with advanced colorectal cancer who have a poor prognosis and are experiencing debilitating symptoms.
1. Hickish T, Andre T, Wyrwicz L, et al. MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2017 Jan 13. doi: 10.1016/S1470-2045(17)30006-2. [Epub ahead of print]