Extended Data Fig. 5. Heterogeneity of radiographic stable disease with respect to ctDNA response and long-term clinical outcomes.

To expand the post hoc analyses of differential outcomes based on ctDNA response for patients with radiographically stable disease on immune checkpoint blockade, we computed the concordance between radiographic and ctDNA responses from previously reported IO cohorts together with BR.36 (Anagnostou et al., Cancer Research, 2019, Bratman et al., Nature Cancer, 2020, Murray et al., Cancer Research, 2021, Sivapalan et al., Clin Cancer Research, 2023). (a) These analyses showed that the concordance between radiographic (CR/PR vs SD/PD) and ctDNA responses depends on the fraction of patients with stable disease, a group that shows heterogeneity with respect to ctDNA responses across all cohorts analyzed (b). (c) Looking at differences in progression-free and overall survival within the radiographically stable patients across studies, ctDNA response accurately captured longer progression-free and overall survival (Anagnostou et al.: median OS = 13.6 for mR vs 13.7 for mPD, logrank p > 0.05; median PFS = 12.3 for mR vs 5.2 for mPD, logrank p = 9.8e-3. Murray et al.: median OS = 23.0 for mR vs 5.9 for mPD, logrank p = 8.0e-4; median PFS = 23.01 for mR vs 2.7 for mPD, logrank p = 4.8e-3). Stable disease annotation was not available for patients from Bratman et al. cohort, while only one patient who received immunotherapy had stable disease in the Sivapalan et al. cohort, resulting in exclusion of these cohorts from panels b and c. Median survival estimates were derived using survival fit function.