Figure 7: DIREct-On enables early forecasting of ultimate outcomes.

A) Probability of PFS for high DIREct-On score (median = 11.69 mo.) patients, actual DCB patients measured by RECIST (median = 11.69 mo.), low DIREct-On score (median = 1.94 mo.) patients, and actual NDB patients measured by RECIST (median = 1.94 mo.) in the combined DIREct Discovery and Validation cohorts (n = 72).

B) Probability of PFS from start of therapy stratified by DIREct-On score (solid line = expected DCB, dashed lines = expected NDB) in patients in the DIREct Discovery and Validation Cohorts treated with PD-1/PD-L1 single-agent blockade (purple), PD-1 and CTLA-4 combination therapy (orange), or the combination of PD-1 and chemotherapy (green).

C) DIREct-On score in the combined DIREct Discovery and Validation Cohorts (indicated by shape and color) stratified by response measured by RECIST and DCB versus NDB. The horizontal line indicates the threshold identified in the discovery cohort to best classify DCB versus NDB.

D) Vignette for patient with high DIREct-On score and stable disease at the first scan.

E) Vignette for patient with low DIREct-On score and stable disease at the first scan.

F) Probability of PFS for high DIREct-On score (median = 10.26 mo.) and low DIREct-On score (median = 3.62 mo.), in those patients with RECIST stable disease at the first available scan in the combined DIREct Discovery and Validation Cohorts (n = 18).

G) Potential application of DIREct-On to personalize immunotherapy in front-line treatment of advanced NSCLC. Patients could begin by receiving single agent PD-(L)1 blockade for one cycle and could then either remain on PD-(L)1 blockade if DIREct-On forecasts durable response or undergo treatment adaptation or escalation if DIREct-On forecasts lack of durable benefit. See also Figure S7.