Reshma Jagsi, MD, and Christian F. Singer, MD, MPH, on Early-Stage Breast Cancer: Adding a Vaccine to Neoadjuvant Systemic Therapy

Reshma: Christian, thank you so much for taking the time to join me today. You recently presented an extraordinarily intriguing study at the ASCO Symposium, and I would love to hear a little bit more about that study. And in particular, can you start by telling me more about the investigational agent that you used and the strategy of a vaccine in this setting, and what took you to that? Christian: We were actually looking on whether the use of a liposomal vaccine called Decemotib would improve pCR in RCB 0/1 in individuals, in females, with early breast cancer who were treated with standard of care treatment. And the standard of care was either conventional chemotherapy, four cycles of AC, and four cycles of docetaxel, or it was neoendocrine therapy. And we had a one-to-one randomization in this phase two study where we offered 50% of the individuals the additional 12 vaccinations with Decemotib. Reshma: Wonderful. Wonderful. And your primary endpoint was then looking at the pathologic outcomes. What patients did you enroll? And what did you find? Christian: Well, we basically enrolled all HER2-negative patients. So it was either Luminal A patients, if they were postmenopausal, who would receive neoendocrine treatment, or triple negative breast cancer patients, or Luminal B tumors, which would then receive neoadjuvant chemotherapy. Reshma: And so what did you find in terms of that primary outcome of looking at the RCB scores? Christian: Well, unfortunately no much difference. We saw a numerical but not statistically significant improvement in RCB 0/1, but there was not a striking finding. In fact, there was no differences whatsoever. There was no difference in safety. There was no difference in adverse events, which was good, but there also was no difference in terms of efficacy when we looked at TCR. Reshma: Sure. And then you continued to follow these patients for survival, and this is where the story gets really interesting. So can you describe for us what you found in that secondary analysis, exploratory analysis? Christian: Out of the 400 patients that we included in our study, we were able to identify 289 individuals in whom long-term follow-up was available. And we then looked at distant recurrence free survival and overall survival. And to our surprise, we found there was a huge difference in distant recurrence free survival. And if you think about it, overall survival was significantly improved in those patients who received Decemotib in addition to neoadjuvant chemotherapy. Reshma: Can you quantify that for us? Because it was really quite an impressive and intriguing, exciting initial finding. Christian: Yeah. After seven years, 83% of individuals who received the Decemotib in addition to neoadjuvant therapy were alive versus 68% who had only received chemotherapy or neoendocrine therapy alone. So a huge difference. In fact, it was a 50% reduction in the risk to develop distant disease. Reshma: So let's reflect on that a little bit. Obviously preliminary findings from an exploratory analysis, but what could be going on here? Can you talk a little bit about how this investigational agent acts? Can you talk about the glycoprotein involved? Where we see it expressed, so we can think a little bit about this. Christian: The Decemotib is a liposomal vaccine which is targeted against MUC1. MUC1 is an epitope that is expressed in more than 90% of breast cancers, but also in other solid tumors. And in fact, there were studies that have been conducted in lung cancer and that seemed to show some kind of efficacy. But until now, no vaccine has ever been shown to have an improvement in distant disease free survival or overall survival at large. And this really is the first sign of an efficacy of a breast cancer vaccine in patients who've already developed breast cancer. Reshma: Very exciting and intriguing. So what are the next steps, both to figure out why this might be so mechanistically, and to take it to the next stage? Christian: Yeah. Well, we're now looking into the expression of MUC1, the epitope, the antigen, of course. And we also look at autoantibodies to see whether those who had actually recurred despite they had received Decemotib, might have had autoantibodies. And this might explain why the vaccine wasn't effective in this population. Reshma: And have you looked at subgroups of your patients by subtype? You said these were all HER2 negative tumors, but you had some that were hormone receptor positive and some that were hormone receptor negative. Christian: Exactly. Well, the effect was most prominent in chemotherapy-treated patients, obviously, because this is where you would see early recurrences, whereas in endocrine-sensitive tumors, and those are really Luminal A tumors in postmenopausal women, you would expect to have recurrences, first of all, significantly less common and then later on. So I'm not surprised that the effect was not that strong in this population, but the most prominent effect was obviously seen in those who received chemotherapy and also had a poorer prognosis. Reshma: And what was the time point that you gave us the survival data? Christian: Well, it was seven years of follow-up. Reshma: Absolutely. So really, really intriguing study. I think a lot of us are excited about what you found and can't wait to see what you do next here to help us drive this field forward. Thank you so much for joining us and for sharing your insights and for leading this incredibly important work for our field and for our patients. Christian: Was a pleasure. Thank you.