Nonconventional patterns of benefit of solid tumors treated with PD-(L)1 inhibitors: a systematic review.

Abstract

The use of immune checkpoint inhibitors in the treatment of solid tumors has been expanding recently. Standard response evaluation criteria are not well suited to evaluate the clinical benefit from these agents. To systematically review the incidence and characteristics of nonconventional patterns of benefit observed in solid tumors treated with immune checkpoint inhibitors. MEDLINE and EMBASE databases have been searched. Moreover, reference lists of relevant articles were checked for cross-references. Clinical studies evaluating PD-(L)1 inhibitors for the management of advanced solid tumors irrespective of the publication status or language. The review author extracted relevant data on the characteristics of participants and the outcomes of the different studies. Nineteen prospective trials with 5404 participants were included. Among patients experiencing RECIST-defined progression and continued treatment beyond progression, rates of response beyond progression ranged from 4 to 10% (of the total number of included patients). These findings were similarly observed regardless of the PD-(L)1 inhibitor used, the disease treated, or the dose used indicating that these findings are part of the inherent characteristics of PD-(L)1 inhibitors for solid tumors. These findings need confirmation from the results of other prospective studies. Many additional ongoing trials were identified evaluating the use of PD-(L)1 inhibitors for the management of solid tumors. Traditional RECIST criteria are not suited for proper assessment of response to PD-(L)1 inhibitors; and more tailored criteria (e.g. immune-related response criteria) should be employed for patients treated with PD-(L)1 inhibitors; moreover in patients with an evidence of disease progression on initial disease evaluation, treatment should not be stopped except after confirmation of progressive disease with a second evaluation at least 4 weeks later.