Impact of performance status on treatment outcomes: A real‐world study of advanced urothelial cancer treated with immune checkpoint inhibitors

Abstract

Background Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0‐1) would correlate with shorter overall survival (OS) in patients receiving ICIs. Methods In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013‐2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested. Results Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04). Conclusions Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first‐line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

“…Anti-PD-(L)1 ICIs also have a role in the first-line setting for cisplatin-unfit patients with high PD-L1 tumors or for platinum (cisplatin and carboplatin)-unfit patients [2]. However, outcomes for those with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) and treatment-resistant tumors remain poor [5,6]. More recently, erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, and enfortumab vedotin, an antibody-drug conjugate against Nectin-4, both received accelerated FDA approval in treatment-refractory aUC [7,8].…”

Immunotherapy‐based combination strategies for advanced urothelial cancer: A long quest

“…The pembrolizumab and acalabrutinib combination treatment arm had a greater percentage of patients with an ECOG PS of 1 (70% vs 57%, respectively) and fewer patients who were treated with prior cisplatin (63% vs 80%, respectively). However, ECOG PS was not shown to be associated with a lower ORR in patients with aUC, 11 and therefore it is very unlikely that the results were affected by this slight imbalance.…”

Beyond Performance Status

“…Meta-analyses of immunotherapy have shown similar overall survival gains regardless of PS [ 32 , 33 ], although they are problematic as they take data from trials that included only small numbers of patients of poor PS [ 34 ]. Also, trials of immunotherapy may show similar overall response rate (ORR) benefits regardless of PS, but this may not be enough to overcome the survival disadvantage of poor PS at the outset [ 35 ]. There are also signals that despite the overall survival gains in lung cancer immunotherapy appearing to be agnostic of patient PS, this may not be true for all subgroups.…”