Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or higher was found to be associated with shorter survival compared with a PS of 0 to 1 among patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab monotherapy, which may have led to the failure to meet the primary endpoint, according to a post hoc analysis published in JAMA Network Open.1
The majority of pivotal clinical trials that contributed to US Food and Drug Administration approval of immune checkpoint inhibitors did not enroll patients with an ECOG PS of 2 or greater. However, an estimated 34% to 48% of patients with advanced NSCLC have a PS of at least 2.
“While oncologists routinely use PS for decisions regarding chemotherapy, rigorous evidence regarding palliative-intent [immune checkpoint inhibitor] use according to PS is still lacking,” the authors wrote. The aim of this study was to evaluate the effect of PS on outcomes with pembrolizumab treatment of advanced NSCLC.
The single-center cohort study included 74 consecutive patients with advanced NSCLC who received palliative pembrolizumab treatment between 2016 and 2019. The primary endpoints were progression-free survival (PFS) and overall survival (OS).
The median age of the cohort was 68.5 years, and 48.7% of patients were women. The ECOG PS was 0 or 1 among 60.8% of patients; 39.2% had a PS of at least 2, which included 5.4% with a PS of 3. Except for age, baseline characteristics were similar between the groups of PS 0 to 1 and 2 or higher. Patients with a PS of at least 2 had an older median age (72 vs 65; P =.003). Median follow-up time was 19.5 months.
Higher PS was associated with lower disease control and shorter survival. Patients with a PS of 2 or higher had a disease control rate of 53.6% compared with 88.4% among patients with a lower PS (P =.002). Objective response rate was similar between the groups at 17.9% and 27.9% among those with a PS of 2 or higher and 0 to 1, respectively (P =.40).
The researchers found that PFS was shorter among patients with a PS of 2 or higher, with a median of 2.3 months compared with 7.9 months with a PS of 0 to 1 (P =.004). An ECOG PS of 2 or higher was identified as an independent risk factor for shorter PFS (hazard ratio [HR], 2.02; 95% CI, 1.09-3.74; P =.03) in a multivariate analysis.
A PS of 2 or higher was also associated with shorter OS, with a median of 4.1 months compared with 23.2 months with a PS of 0 to 1 (P <.001). In multivariate analysis, a PS of 2 or higher was an independent risk factor for shorter OS (HR, 2.87; 95% CI, 1.40-5.89; P =.004).
The authors concluded that “ECOG PS score of at least 2 was associated with poorer prognosis.” They added that “these findings underscore the importance of further evaluation of the effect of PS on survival outcomes in patients with advanced cancer treated with [immune checkpoint inhibitors] in palliative-intent settings.”
Sehgal K, Gill RR, Wadick P, et al. Association of performance status with survival in patients with advanced non–small cell lung cancer treated with pembrolizumab monotherapy. JAMA Netw Open. 2021;4:e2037120. doi:10.1001/jamanetworkopen.2020.37120