Results showed that recurrence-free survival was actually shorter, by more than 5 months, with the vaccine versus placebo. In addition, the 3-year rate of overall survival was lower by an absolute 10%. Interestingly, tumor expression of MUC1 did not influence benefit from the vaccine.
But Dr. Schimanski noted that survival was better than expected at the trial’s outset. For example, the 65-month median overall survival among all patients in LICC undergoing secondary resection was about a year longer than that of similar patients in the CELIM trial (54 months) and the FIRE-3 trial (56 months).
“The LICC trial failed to meet its primary endpoint of significantly improving recurrence-free survival or overall survival with tecemotide. We had unexpectedly high overall survival in both arms, highlighting the critical importance of accurate staging and intensive surveillance, in our eyes,” he concluded. “We have further analysis of a very large translational program, and we hope to learn a lot about recurrence independent of tecemotide.”
A good space for testing immune therapies
In 2009, a consensus panel of immunologists ranked MUC1 as the second-best cancer antigen for translational research, “so there was clearly a feeling that this was a good target at that time for going forward,” noted invited discussant Michael J. Overman, MD, a professor in the department of gastrointestinal medical oncology, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston.
Dr. Michael J. Overman
He agreed with the LICC investigators’ conclusions that the trial was negative and that MUC1 expression does not appear to predict outcome. “Whether that’s the wrong target, or whether it was the wrong formulation in regards to cancer vaccine, I think we do not know. I do think that survival was encouraging,” he said.
“There’s many unanswered questions in regards to the LICC study and in regards to cancer vaccines in general,” Dr. Overman noted. Among them, what are the optimal antigens to target, what are the optimal vaccine formulations and adjuvant agents, what is the best way to address the immunosuppressive tumor microenvironment, and what is the correct disease setting for vaccine testing?
“The LICC study is very impressive in demonstrating that we can enroll in this posthepatectomy space, postmetastectomy space. It’s a very increasingly interesting space for, potentially, drug development and immunologic exploration,” he maintained. “One of the benefits of this space when we talk about a minimal residual disease setting is that you potentially do not have the suppressive effects from the tumor microenvironment that potentially are hindering success in regards to having immune therapy response. So I would say that this is a space we should consider for drug development going forward.”