Abstract 7500: START: A Phase III Study of L-BLP25 Cancer Immunotherapy for Unresectable Stage III Non-Small Cell Lung Cancer Charles Andrew Butts, et al.
START: A new beginning?
As the 2013 ASCO annual meeting was revealing important results on the immunotherapy of cancer (mainly targeting CTLA-4 and PD1), the START trial was also the object of a presentation. The objective of the trial (Figure 1) was to evaluate the effect of a passive immunization with BLP-25 (a MUC-1-based vaccine) in patients with tumor control with chemoratiation therapy for Stage III NSCLC. The Phase III was initiated after a randomized Phase IIB demonstrated that the subgroup of patients with Stage IIIB derived a significant survival advantage in a retrospective analysis. Unfortunately, START did not achieve the primary objective of increasing median OS by six months as aimed in the statistical plan, although there was an important trend (Figure 2). Looking back at the patient population that did well in the Phase IIB trial, patients treated with concurrent chemoradiation therapy demonstrated a statistically significant survival advantage (Figure 3). It is good to see/note that the concurrent Ch/RT arm placebo arm was exactly what one would have predicted in terms of survival (therefore a reasonable standard control arm to act as a baseline comparator). Irrespective of statistics, in terms of patient number enrolled the concurrent Ch/RT portion of the trial is actually larger than any other Stage III NSCLC trial to date (n = 806 patients).
One has to wonder if these results should lead to the acceptation of this new therapy. Clearly, this group of patients with a high event rate of death needs new therapy options, and the BLP-25 vaccination trial is probably one of the investigational therapies that achieved the greatest increase in median Overal Survival if patients were initially treated with concurrent chemoradiation. Regardless, the FDA is unlikely to approve the vaccine based on this trial alone (as primary end point not met, irrespective of size or statistical significance of the Ch/RT + vaccine subgroup). The oncology community should take a hard look at these results and decide if confirmatory analyses are necessary or if the correlative studies that have been done in the START trial will give more information/confirmation on which patient population to treat specifically.
For our patients (and the lung cancer treating oncology community at hand) consideration for a concurrent Ch/RT + vaccine vs. concurrent Ch/RT trial is fully justified in terms of understanding/improving patient outcomes. The question remains however, if Merck (or others) will fund such a needed trial. Merck is still testing the vaccine in smaller (425 patients) trial in Asia called INSPIRE (http://clinicaltrials.gov/show/NCT01015443) — but different patient population, Ch/RT regimens and results not expected soon.