Pembrolizumab monotherapy for untreated PD-L1-Positive non-small cell lung cancer in the elderly or those with poor performance status: A prospective observational study

Abstract

ObjectivesWe investigated the efficacy and safety of pembrolizumab monotherapy as first-line treatment for poor Eastern Cooperative Oncology Group performance status (PS) and elderly patients with programmed cell death-ligand 1 (PD-L1)-positive advanced non-small cell lung cancer (NSCLC). We also investigated clinical prognostic factors for the efficacy of pembrolizumab monotherapy, based on patient characteristics.Materials and methodsIn this prospective observational study, PS-2 and elderly NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1% who received first-line pembrolizumab monotherapy, from October 2019 to March 2021, at 10 institutions in Japan were enrolled. Patients judged eligible by their physicians for combined chemotherapy and PD-1/PD-L1 inhibitors as first-line treatment were excluded. Clinicopathological characteristics and adverse events were investigated for correlation with clinical outcomes.ResultsForty patients were enrolled in the study. The median progression-free survival (PFS) of patients with PS 2 and those aged ≥ 75 years were 4.4 (95% confidence interval [CI]: 0.9–14.4) months and 5.3 (95% CI 2.9–9.4) months, respectively. The median overall survival (OS) of patients with PS 2 and those aged ≥ 75 years were 11.6 (95% CI: 1.4–not evaluable [NE]) months and 11.6 (95% CI 7.4–18.1) months, respectively. Immune-related adverse events (irAEs) were observed in 19 patients; 6 patients had severe irAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher. Patients who achieved stable disease or better, had a statistically significant increase in PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, the acquisition of disease control with pembrolizumab monotherapy was an independent prognostic factor for PFS and OS.ConclusionPembrolizumab monotherapy was relatively effective and tolerable as a first-line treatment for patients with PD-L1-positive advanced NSCLC who had poor PS or were elderly. Our results suggest that disease control might be an independent prognostic factor for PFS and OS in this population. (UMIN000044052 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050176)

Three-Year Overall Survival of Patients With Advanced Non–Small-Cell Lung Cancers With ≥50% PD-L1 Expression Treated With First-Line Pembrolizumab Monotherapy in a Real-World Setting (ESCKEYP GFPC Study)

“…After a median follow-up of 34 months, the median real-world time on first-line pembrolizumab monotherapy was 7.4 (6.3–8.1) months for the entire cohort but only 2.1 (1.4–2.8) months for the 237 patients with ECOG PS = 2 12 . The same effect was also observed in a multicenter Japanese study on 40 elderly patients (median age 78.5 y) and/or ECOG PS = 2 (40%); 9 the objective response rate was 40.5% and the disease-control rate was 62%. After a median (95% CI) follow-up of 9.5 (0.3–27.1) months, median PFS and OS for patients ≥75 years old were, respectively, 5.3 (2.9–9.4) and 11.6 (7.4–18.1) months, with respective durations for those with ECOG PS = 2 of 4.4 (0.9–14.4) and 11.6 (1.4–NR) months.…”

“…According to the findings of those 2 studies, ECOG PS ≥2 was an independent factor associated with poorer OS 3,4 . That observation was echoed in other reports 5–12 . The results of a prospective, observational study on 40 patients with ECOG PS = 2 or ≥75 years old, with ≥1% PD-L1 expression on their aNSCLC cells showed that median (95% CI) OS on first-line pembrolizumab lasted 11.6 (1.4–NR) months for patients with ECOG PS = 2 and 11.6 (7.4–18.1) months for the elderly 9 .…”

“…[5][6][7][8][9][10][11][12] The results of a prospective, observational study on 40 patients with ECOG PS = 2 or ≥ 75 years old, with ≥ 1% PD-L1 expression on their aNSCLC cells showed that median (95% CI) OS on first-line pembrolizumab lasted 11.6 (1.4-NR) months for patients with ECOG PS = 2 and 11.6 (7.4-18.1) months for the elderly. 9 However, long-term, real-world efficacy data for pembrolizumab in this indication are scarcer. 12 The objective of this study was to evaluate, in the long term, the efficacy of pembrolizumab monotherapy in a realworld setting in patients with aNSCLC expressing ≥ 50% PD-L1.…”

“…3,4 That observation was echoed in other reports. [5][6][7][8][9][10][11][12] The results of a prospective, observational study on 40 patients with ECOG PS = 2 or ≥ 75 years old, with ≥ 1% PD-L1 expression on their aNSCLC cells showed that median (95% CI) OS on first-line pembrolizumab lasted 11.6 (1.4-NR) months for patients with ECOG PS = 2 and 11.6 (7.4-18.1) months for the elderly. 9 However, long-term, real-world efficacy data for pembrolizumab in this indication are scarcer.…”

Concomitant Proton Pump Inhibitor Use With Pembrolizumab Monotherapy vs Immune Checkpoint Inhibitor Plus Chemotherapy in Patients With Non−Small Cell Lung Cancer

“…However, whether ICI plus chemotherapy is effective and safe for frail patients, such as older patients or those with poor ECOG PS, remains uncertain . In contrast, several previous studies have shown the efficacy and safety of pembrolizumab monotherapy in these frail populations; therefore, pembrolizumab monotherapy may be a more reasonable treatment option than ICI plus chemotherapy for frail patients with NSCLC with high PD-L1 TPS in a clinical setting. Considering the treatment strategy for these clinical patients, we should recognize that PPI use may be negatively associated with the treatment outcome of ICI monotherapy.…”