Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy

Abstract

<b><i>Background:</i></b> Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. <b><i>Methods:</i></b> We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. <b><i>Results:</i></b> Linear regression analyses and Spearman’s rank correlation coefficient revealed that PPS was strongly correlated with OS (<i>r</i> = 0.76, <i>p</i> < 0.05, <i>R</i><sup>2</sup> = 0.65), while PFS was only moderately correlated with OS (<i>r</i> = 0.71, <i>p</i> < 0.05, and <i>R</i><sup>2</sup> = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both <i>p</i> < 0.05). <b><i>Conclusions:</i></b> Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.

Post‐progression survival after atezolizumab plus carboplatin and etoposide as first‐line chemotherapy in small cell lung cancer has a significant impact on overall survival

“…11 Several studies found that PPS following first-line chemotherapy for advanced NSCLC at the clinical trial level is strongly correlated with OS; 14,15 similar studies examined the impact of PPS in ED-SCLC and advanced NSCLC based on individual patient-level analysis of the strong correlation between OS and PPS. [16][17][18][19]28,29 In contrast to the previous reports, 26,27 we found that PFS does not necessarily reflect OS in patients with ED-SCLC treated with AteCE, but rather that PPS strongly influences OS. The results show that PFS is shorter than PPS, PPS influences OS intimately, and the relationship is linear.…”

“…Before receiving therapy, all patients underwent systematic evaluation and standardized staging procedures. The clinical stage was assigned based on the results of physical examination, chest radiography, thoracic and abdominal computed tomography (CT), brain magnetic resonance imaging or CT, and bone scintigraphy or 18 Ffluorodeoxyglucose positron emission tomography to assess the tumor-node-metastasis (TNM) stage. Clinical stage III/IV SCLC was evaluated per the Union for International Cancer Control TNM classification, eighth edition.…”

“…In non‐small‐cell lung cancer (NSCLC), prolonged PFS does not necessarily translate to prolonged OS, 13 but post‐progression survival (PPS) is highly correlated with OS beyond first‐line treatment 14,15 . Several studies with individual‐level analysis have reported that PPS after first‐line treatment is strongly correlated with OS in metastatic NSCLC 16–18 . Moreover, OS is represented by the summation of PFS and PPS 11 .…”

“… 14 , 15 Several studies with individual‐level analysis have reported that PPS after first‐line treatment is strongly correlated with OS in metastatic NSCLC. 16 , 17 , 18 Moreover, OS is represented by the summation of PFS and PPS. 11 A strong correlation between PPS and OS following treatment with carboplatin and etoposide as first‐line chemotherapy for patients with ED‐SCLC has been previously reported based on individual‐level data.…”

IFN-Gamma Expression in the Tumor Microenvironment and CD8-Positive Tumor-Infiltrating Lymphocytes as Prognostic Markers in Urothelial Cancer Patients Receiving Pembrolizumab

“…Survival was analyzed using the Kaplan–Meier method and Cox regression analysis. The correlations among OS, PFS, and PPS were assessed by Spearman’s rank correlation coefficients and linear regression analyses without censored cases as described previously [ 26 ]. The correlations for survival were also tested using data from 450 metastatic urothelial carcinoma cases treated with pembrolizumab in another study cohort [ 27 ].…”