Developing an Effective Breast Cancer Vaccine

Hatem Soliman, MD


Cancer Control. 2010;17(3):183-190. 

In This Article

Paradigms for Clinical Vaccine Development

Since the clinical effect of cancer vaccines differs from that shown with cytotoxic agents, the clinical development paradigm for vaccines should also be different. Concepts such as a maximally tolerated dose or response rates measured by traditional response evaluation criteria in solid tumors (RECIST) criteria may not apply to early-phase cancer vaccine trials. Also, heterogeneity in immunologic monitoring tests makes it difficult to standardize definitions of immunologic efficacy. There has been a significant effort to define pathways and harmonized methods for translational cancer immunotherapy. The Translational Research Working Group published a recommended pathway incorporating various milestones in a flowchart algorithm for translating potential immunologic therapies from the bench to its use in clinical trials.[11] For vaccines that are ready for clinical testing, a useful guide for appropriate clinical trial design was published in 2007 by the Cancer Vaccine Clinical Trial Working Group.[12] Rather than performing the usual phase I-III trials, recommendations include carrying out proof-of-principle trials followed by efficacy trials for promising candidates. A proof-of-principle trial would enroll approximately 20 to 30 patients to allow for safety, limited dose ranging, and immunologic efficacy testing. Efficacy trials should be randomized trials that can be a hybrid of a phase II/III trial with well-defined time-to-event endpoints such as overall, disease-free, and progression-free survival. When using progression-free survival as an endpoint, patients with minor progression (ie, < 50% increase in overall tumor burden or < 3 new lesions) at their first evaluation time point should be allowed to continue to the next evaluation time point. This is because patients treated with cancer vaccines may show early progression followed by a delayed response to treatment. Response patterns to ipilimumab, the anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibody, have been described as immediate, late (after progression), or response of the target lesions in the presence of new lesions. To better describe the clinical effects of this novel treatment and take these variable responses into account, some trials have used modified response criteria such as the immune-related response criteria based on the modified World Health Organization measures.[6] A similar guideline titled Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines has been recently drafted by the International Society for the Biological Therapy of Cancer and the FDA ( to define best practices for immune monitoring tests and immunotherapy biomarkers.[13] Until this is finalized, published recommendations on harmonization of the enzyme-linked immunospot (ELISPOT) tetramer methods are available that provide a good foundation for conducting correlative immunologic testing.[14–16] Overall, these efforts should provide investigators with a way to harmonize immunotherapy trials using an accepted standard for trial design and immune response monitoring.


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