Patterns of outcomes and the relevance surrogate endpoints in patients treated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy because of their ability to induce tolerable and durable responses in advanced cancers. This can be attributed to the unique mechanism by which ICIs trigger a person’s immune system to reject cancer cells. The effects of ICIs in patients are different from those observed with conventional chemotherapies. For instance, while chemotherapy typically causes cancer cell death resulting in detectable shrinkage of cancers, ICIs may stop or slow cancer growth for long periods without evidence of cancer cell death. In several small studies, patients treated with ICIs have also been noted to have prolonged lives despite their cancers growing during ICI treatment. The different patterns of responses observed in patients treated with ICIs are important to recognize as they guide expectations of treatment outcomes for patients and may inform the design of clinical trials studying ICIs. However, atypical responses to ICIs have not been consistently defined in past studies or only assessed at the level of trials. This is also of clinical relevance as surrogate endpoints, substitute measures of overall survival, are frequently used in ICI trials to determine the advancement of treatment testing or for FDA approval.

Our primary objective is to assess how objective response categories, progression-free survival (PFS), duration of response (DUR), time to best response (TTBR), and depth of response (DepOR) are associated/correlated with overall survival (OS) in patients treated with ICIs.