Parikh RB, Min EJ, Wileyto EP, et al. - For cases with many advanced solid tumors, standard of care include immune checkpoint inhibitors (ICIs). Patients exhibiting poor performance status or organ dysfunction are conventionally ineligible to participate in pivotal randomized clinical trials of ICIs. This research was undertaken to evaluate ICI use as well as survival results in patients with advanced cancers who are traditionally trial ineligible based on poor performance status or organ dysfunction.

• This cohort study included 34,131 patients with cancer (9318 [27.3%] trial ineligible) who started first-line systemic therapy for newly diagnosed metastatic or recurrent nontargetable non–small cell lung, urothelial cell, renal cell, or hepatocellular carcinoma.

• A greater probability of ICI monotherapy use, vs non-ICI therapy, was observed in relation to trial ineligibility (inverse probability–weighted-adjusted odds ratio vs non-ICI therapy, 1.8; 95% CI, 1.7-1.9).

• No overall survival differences were found between treatment with ICI monotherapy, ICI combination therapy, and non-ICI therapy, among trial-ineligible patients.

• Overall, trial-ineligible patients with advanced malignancies, vs trial-eligible patients, preferentially received first-line ICI therapy.

• Phase 3 trials-generated positive outcomes for ICI treatment may not translate to patients with poor performance status or organ dysfunction who are conventionally ineligible for such trials.