Fig. 1: Trial design.

a, The ProBio platform design, including control and investigational arms, with adaptive randomization after screening and ctDNA analysis. Upon reaching progression, patients were re-randomized. Follow-up and treatment response evaluation followed the PCWG3 recommendations. Investigational arms in transparent gray denote other investigational arms to which patients could have been randomized, which do not fall within the scope of the current paper. b, The CONSORT diagram detailing patient screening, randomization and follow-up. Inclusion and randomization updated until 25 November 2022, with results for ARPIs and taxanes. Data on other investigational arms pending. As of this date, 7 patients awaited liquid biopsy results and had not been randomized. An extra 4 months of follow-up were allowed until March 2023 for 193 randomized patients. Of 129 patients in the investigational arms, 49 reached the progression endpoint, remained in the trial, and were re-randomized. In the physician’s choice group, 28 of 64 patients continued with new standard-of-care treatments. Follow-up included all-cause mortality from electronic health records. MSI+, microsatellite instability positive.