Bayesian predictive probability, sample size, and protocol modifications
toxicity, TNBC
Considering different degrees of enrollment efficiency and different population distributions among the treatment arms, we used the Bayesian predictive probability approach to lay out an adaptive design in the new protocol amendment (July 24, 2020). This study was originally designed to have 10–20 patients enrolled in each arm, bringing the estimated sample size to approximately 140 patients. Referring to the historical data of heavily pretreated TNBC patients after multiline chemotherapy,Due to the difficulty of enrollment and the promising efficacy observed in other arms in the interim analysis, arms A and G could be terminated early at fewer than 10 patients (more details in Supplementary information, Data Some modifications have been made in the new version of protocol, and we briefly summarized them as follows: (1) the sample sizes in each arm were set to be more flexible according to Bayesian prediction probability method, and the rationale behind it was explained as above, (2) CTCAE version 4.0 was updated to version 5.0, (3) bevacizumab or low dose VEGFR inhibitors have been explored due to the toxicity issues with the VEGFR inhibitors.The study design allowed arms to be dynamic so that old arms could be eliminated when finished and new arms could be added. Notably, the investigators used FUTURE as a platform to test the safety and efficacy of potential new drug–biomarker combinations in heavily pretreated TNBC patients.