Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population

Abstract

The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.

Clinical Effectiveness of Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with a Poor Performance Status

“…Moreover, Santini et al described that a higher proportion of NSCLC patients who had received ICIs within 30 days of death had a PS ≥ 2 [30]. Jiménez Galán et al also examined the clinical efficacy of the NSCLC patients receiving pembrolizumab as firstline treatment according to the level of the ECOG PS using a single-center retrospective study [31]. In their study, the ORR, median PFS, and median OS in the patients with an ECOG PS 0-1 and an ECOG PS ≥ 2 were 26.1 and 5.7% (p = 0.014), respectively; 9.6 and 1.6 months (p < 0.001), respectively; and 18.9 and 2.0 months (p < 0.001), respectively [31].…”

“…Jiménez Galán et al also examined the clinical efficacy of the NSCLC patients receiving pembrolizumab as firstline treatment according to the level of the ECOG PS using a single-center retrospective study [31]. In their study, the ORR, median PFS, and median OS in the patients with an ECOG PS 0-1 and an ECOG PS ≥ 2 were 26.1 and 5.7% (p = 0.014), respectively; 9.6 and 1.6 months (p < 0.001), respectively; and 18.9 and 2.0 months (p < 0.001), respectively [31]. They concluded that the ECOG PS was a single independent predictor of the OS and PFS found in their study.…”

Impact of Frailty on Outcomes of First-Line Pembrolizumab Monotherapy in a Real-World Population with Advanced Non-Small Cell Lung Cancer

“…ECOG PS has been identified as a prognostic factor of survival in patients with NSCLC treated with pembrolizumab in a first-line setting [33,34]. In a previously published study [15], we found that patients treated with pembrolizumab with ECOG PS ≥ 2 had a significantly shorter OS and PFS than those with ECOG PS of 0-1, with a median OS of 2 months and 18.9 months, respectively. However, the use of the ECOG as a prognostic marker is insufficient, and it is necessary to investigate other aspects related to the patient.…”

“…These findings have been shown in real-world data studies because clinical trials have excluded patients with PS ≥ 2 [13,14]. We recently published a study with real-life data in which patients with non-small lung cancer (NSCLC) and PS of 0-1 treated with pembrolizumab in a first-line setting had better clinical outcomes than patients with ECOG PS ≥ 2 [15]. This scale is the one most commonly used in cancer patients to assess their disability level.…”

“…This was a cohort expansion of a previously published observational, single-center, retrospective study [15] that included all patients with advanced NSCLC with a PD-L1 Tumor Proportion Score (TPS) ≥ 50% and negative mutations of EGFR (epidermal growth factor receptor) or ALK (anaplastic lymphoma kinase) treated with pembrolizumab singledrug therapy as first-line treatment between 1 January 2017 and 31 December 2020.…”