A trial of an antigen-specific cancer vaccine known as tecemotide failed to improve outcomes over placebo in patients with colorectal cancer and liver metastases. Though there was a biological rationale for targeting the MUC1 antigen, this trial suggests that it may not be a suitable target in this malignancy.
As many as 35% of colorectal cancer patients have distant metastases at diagnosis. “Hepatic metastasectomy is deemed the only potential curative treatment for stage IV colorectal cancer limited to liver metastases,” said Carl C. Schimanski, MD, PhD, of Klinikum Darmstadt GmbH in Darmstadt, Germany. “High recurrence rate after resection remains a major challenge.”
Schimanski presented results of the LICC trial at the American Society of Clinical Oncology (ASCO) 2019 Gastrointestinal Cancers Symposium, held January 17–19 in San Francisco (Abstract 480). The study tested tecemotide, which targets the cancer antigen MUC1, following cyclophosphamide, compared with saline followed by placebo. A total of 121 patients were randomized, but after exclusions for several reasons, there were 61 patients in the tecemotide group and 33 in the placebo group.
All patients had stage IV colorectal cancer with metastases limited to the liver. Baseline characteristics were generally well balanced, though more people in the vaccine group had an ECOG performance status score of 0.
The median recurrence-free survival (RFS) was 6.1 months with tecemotide, and 11.4 months with placebo; this difference was not statistically significant. The median overall survival (OS) was 62.8 months with the vaccine, and the median was not yet reached with placebo; the 3-year OS rate was 69.1% with tecemotide and 79.1% with placebo. This again was not statistically significant, but Schimanski noted that these were unexpectedly high OS rates given the patient population; this likely reflected the careful staging and tight surveillance program built into the design of the trial.
Grade 3 or 4 treatment-emergent adverse events were relatively infrequent in both groups. Treatment-emergent adverse events of any grade were more common in the tecemotide group, with the most common including nausea (30.4% vs 19.0%), fatigue (24.1% vs 19.0%), and diarrhea (19.0% vs 16.7%).
“The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with tecemotide,” Schimanski concluded. “MUC1 expression was not associated with outcome….We have to conclude that the target is not really validated.”
Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center in Houston, was the discussant for the study, and he agreed that the results are clearly negative. “Whether it’s the wrong target or the wrong formulation, I think we do not know,” he said.
He added, though, that the study does show it is feasible to recruit patients to trials in the post-metastasectomy setting, which could have advantages, especially with immuno-oncologic approaches. “You potentially do not have the suppressive effects from the tumor microenvironment that potentially are hindering success with regards to an immunotherapy response,” he said. “I think there is a lot of potential to evaluate and investigate new drugs in this setting.”