Prognostic and treatment-predictive factors—is there a difference?

Abstract

The terms risk factor, prognostic factor and predictive factor are often imprecisely used. We de®ned a prognostic factor as a patient characteristic that identi®es subgroups of untreated patients having different outcomes, and a factor predictive of treatment effect as a patient characteristic that identi®es subgroups of treated patients having different (as a consequence of treatment) outcomes. To illustrate this, theoretical graphical examples were constructed and data from the literature on prostate cancer were used to substantiate the theoretical examples. In most situations, but not necessarily always, a prognostic factor is also predictive of the effect of speci®c treatments. Whether a prognostic factor is also predictive of treatment effect or not can only be assessed in a valid comparative setting such as in a randomized trial. A factor that is predictive for treatment effect may not be predictive for another treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 265±268.

Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies

“…A prognostic factor is a clinical, laboratory, or molecular variable that correlates with the natural course of the disease regardless of treatment, whereas a predictive factor is a variable used to identify subpopulations of patients who are most likely to benefit from a specific treatment. 20 Some treatment algorithms are being based only on prognostic factors identified from retrospective analyses and real practice rather than on purely predictive factors for treatment-based multivariate analysis of data from randomized controlled studies. 5,21,22 Moreover, elucidation of predictive factors of response is key to designing and analyzing current and future clinical trials where sorafenib may be the comparator.…”

Characterizing Exposure–Response Relationship for Therapeutic Monoclonal Antibodies in Immuno‐Oncology and Beyond: Challenges, Perspectives, and Prospects

“…Based on their interaction with the treatment, baseline factors can be classified as prognostic or predictive factors. [42][43][44] During the treatment, baseline predictive factors either become PD factors (or drug target) or modulate PD factors (Figure 1c, component 2b). Thus, predictive factors can directly or indirectly interact with drug treatment (via exposure) and lead to enhanced treatment response (disease modification) in the treatment group but may exacerbate the disease progression in the control group.…”

“…14,45,46 Of note, some prognostic factors can also be predictive factors and are expected to have different effects to some degree between the treatment arm and the control arm. [42][43][44] Because prognostic factors have similar effects in two arms, matched prognostic factors should have a zero net effect on HR within paired subgroups, and across exposure subgroups even if they are imbalanced across them. In contrast, predictive factors would not have net zero effect on HR even if they are matched within paired subgroups.…”

“…MET‐positive patients or high‐PDL1 expressors have shown to be associated with a shorter survival in chemotherapy but associated with a longer survival with MET inhibitor or anti‐PD1/PDL1 treatment compared with MET‐negative subjects or low‐PDL1 expressors 14,45,46 . Of note, some prognostic factors can also be predictive factors and are expected to have different effects to some degree between the treatment arm and the control arm 42–44 . Because prognostic factors have similar effects in two arms, matched prognostic factors should have a zero net effect on HR within paired subgroups, and across exposure subgroups even if they are imbalanced across them.…”

Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma

“…Despite the expansion of correlative studies, currently most cannot discriminate between the identification of predictive or prognostic biomarkers. In part, this issue is due to significant advances both in technologies since natural history studies were done, and revolutionary changes in therapies 11,12 .…”