How many immunotherapy trials in breast cancer translate into positive phase III trials?

A new Italian study from researchers of Università Vita-Salute San Raffaele di Milano and Fondazione Michelangelo, recently published on JAMA Network Open, shows that many immunotherapy trials in breast cancer fail to translate into positive phase III trials and highlights the key factors mostly related to low-yield studies.

Authors aimed to survey the immunotherapy clinical trial landscape of breast cancer in order to examine what proportion of trials failed to report outcome and what proportion yielded positive results, describing trial features associated with these two outcomes. A total of 331 immuno-oncology trials were initiated in breast cancer by April 2023; 47 were phase I, 242 trials were phase II and 42 phase III; authors evaluated how many of them reported their results, either as an abstract or manuscript, and categorized the trials as positive or negative if they met their endpoints or not, respectively. One hundred twenty trials had primary completion dates up to November 30, 2022, of which 30 (25%, enrolling a combined 2428 patients) failed to report their outcomes; 7 phase I trials (31.8%), 21 phase II trials (23.6%), and 2 phase III trials (22.2%) were unreported. Single-center studies were significantly more likely to be unreported than multicenter studies (35% vs 15%, respectively); small studies and non-randomized phase II trial are the most low-yield one. «Results from phase II trials are supposed to guide phase III trial design to maximize the chance for positive outcome. Disappointingly, 89.5% of the completed randomized immunotherapy trials yielded negative results», authors say. «The large number of immunotherapy trials being run have yielded modest clinical impact. Single-center studies commonly fail to report outcome, and the many phase II studies that have been conducted have not translated into many successful phase III trials. More selective initiation of phase II trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency», authors conclude.