Pembrolizumab-combination therapy for previously untreated metastatic nonsquamous NSCLC: Real-world outcomes at US oncology practices

Abstract

ObjectivesThe availability of immunotherapies has expanded the options for treating metastatic NSCLC, but information is needed regarding outcomes of immunotherapy for patients treated outside of clinical trials. The aim of this retrospective study was to evaluate the outcomes of therapy with first-line pembrolizumab plus pemetrexed and carboplatin (pembrolizumab-combination) for patients with metastatic nonsquamous NSCLC in the real-world setting of oncology clinics in the United States (US).MethodsUsing deidentified, longitudinal patient records from a nationwide, electronic health record-derived US database, we identified patients with metastatic nonsquamous NSCLC, without EGFR/ALK/ROS1 genomic alterations, who had received no previous systemic anticancer therapy. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and initiated first-line pembrolizumab-combination therapy from 11-May-2017 to 31-January-2019; data cutoff was 31-August-2020. Patients treated in a clinical trial were excluded. Manual chart review supplemented technology-enabled abstraction to identify disease progression and tumor response. Time-to-event endpoints from initiation of pembrolizumab-combination therapy were determined using Kaplan-Meier.ResultsOf 377 patients with metastatic nonsquamous NSCLC, 105 (28%), 104 (28%), and 103 (27%) had programmed death-ligand 1 (PD-L1) expression ≥50%, 1–49%, and <1%, respectively; PD-L1 expression was not documented for 65 patients (17%). Median age was 66 years, and 227 patients (60%) were men. Median follow-up time from first-line therapy initiation to data cutoff was 31.2 months (range, 19.0-39.6 months). Median pembrolizumab real-world time on treatment (rwToT) was 5.8 months (95% CI, 5.0-6.7); 12- and 24-month on-treatment rates for pembrolizumab were 28.0% and 14.9%, respectively. Median overall survival (OS) was 17.2 months (95% CI, 13.6-19.9). For patients in PD-L1 expression ≥50%, 1-49%, <1%, and unknown cohorts, the 12-month survival rates were 66.0%, 58.5%, 54.5%, and 58.3%, respectively, and 24-month survival rates were 43.1%, 37.2%, 35.6%, and 42.0%, respectively. Median real-world progression-free survival was 6.2 months (95% CI, 5.5-7.1); and the real-world response rate was 39.3%, with median duration of response of 13.1 months (95% CI, 10.5-16.8).ConclusionsThese findings demonstrate the benefits of first-line pembrolizumab-combination therapy for patients with EGFR/ALK-wild-type, metastatic nonsquamous NSCLC and good performance status who are treated at US community oncology clinics.

Non-Small-Cell Lung Cancer Immunotherapy and Sleep Characteristics: The Crossroad for Optimal Survival

“…All newly diagnosed patients had poor sleep quality, which was associated with daily fatigue. As previously observed in other immunotherapy studies, patients with high a PD-L1 status (≥80%) have a faster response and a prolonged response [ 24 ]. We stratified our patients, as in previous studies, into three categories in order to perform our analysis [ 25 , 26 ].…”

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy

“…Somewhat lower survival rates than in the clinical trials and our analysis were reported in two analyses based on the US Flatiron Health Database, with a median OS of 9.3-12.0 months [31][32]. From the same database, a median OS of 17.2 months was reported for PD-(L)1 combination therapy in NSQ NSCLC [33]. Major differences with the current study include geography, complete information on ECOG PS in the present study, and that our study is population-based, unlike database studies only including patients from a specific US electronic health record system.…”

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice

“…In the subgroup of patients with expression of PD-L1 <1%, the objective response rate was 26%, median PFS was 5 months (95%CI 4.5-6.2) and the median OS was 13.2 months (95%CI 10.9-19.9). In the subgroup with expression of PD-L1 in the range of 1-49%, median OS was 16.0 months (95% CI 11.7-22.1); it was not indicated whether observed differences were statistically significant ( 20 ), but the difference is meaningful numerically. In the above study, among patients with negative PD-L1 expression, 41% of patients received systemic treatment after failure of immunochemotherapy, a slightly higher proportion than in our group (31%) and in the previously cited study by Waterhouse et al.…”

“…Liu et al. presented a group of 377 patients with non-squamous metastatic NSCLC – 24% of the patients did not have an evaluation of PD-L1 expression, and 27% had low PD-L1 expression ( 20 ). The median overall survival (OS) was 17.2 months (95% CI, 13.6-19.9) in the general population.…”