Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data

Abstract

Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0–2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan–Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3–8.1) for 807 patients with PS 0–1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4–2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0–1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.

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)

“…The negative effect of ECOG PS = 2 was also found in an American study based on deidentified electronic medical record data. 12 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%.…”

“…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.…”

A Machine Learning Approach to Real‐World Time to Treatment Discontinuation Prediction

“…[3] It is often used as a surrogate effectiveness endpoint, showing a high correlation to progressionfree survival and a moderate-to-high correlation to overall survival. [4,5] As rwTTD is an important metric for drug effectiveness, it is routinely reported during the postclinical trial phase. [2,4,[6][7][8] Calculation of rwTTD in patient population is often equivalent to constructing a Kaplan-Meier (KM) curve, with each point representing the proportion of patients that are still on treatment at a specific time point.…”

“…[ 3 ] It is often used as a surrogate effectiveness endpoint, showing a high correlation to progression‐free survival and a moderate‐to‐high correlation to overall survival. [ 4,5 ] As rwTTD is an important metric for drug effectiveness, it is routinely reported during the post‐clinical trial phase. [ 2,4,6–8 ]…”

A Machine Learning Approach to Real-world Time to Treatment Discontinuation Prediction

“…Because time to treatment discontinuation can be readily obtained from electronic medical records, this effectiveness endpoint is convenient to evaluate the efficacy of a drug that is already approved for public use 3 . It is often used as a surrogate effectiveness endpoint, showing high correlation to progression-free survival and moderate-to-high correlation to overall survival 4,5 . As rwTTD is an important metric for drug effectiveness, it is routinely reported during the post-clinical trial phase 2,4,[6][7][8][9] .…”