Abstract
Initial approval for immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC) was limited to patients with high levels of programmed cell death ligand 1 (PD-L1) expression. However, in the period after approval, it is not known how new evidence supporting efficacy of these treatments in patients with low or negative PD-L1 expression was incorporated into real-world practice. To evaluate the association between PD-L1 testing and first-line ICI use. This retrospective cohort study (January 1, 2011, to December 31, 2018) used a deidentified nationwide electronic health record-derived database reflecting real-world care at more than 280 US community and academic cancer clinics (approximately 800 sites of care). Patients included those with advanced NSCLC without other identifiable variations diagnosed in the period after the US Food and Drug Administration's initial first-line approval of ICIs for patients with high PD-L1 expression (≥50%). First-line ICI treatment. Patterns of PD-L1 testing and first-line ICI treatment among all patients and patients stratified by tumor histologic type (squamous vs nonsquamous). A total of 45 631 patients (mean [SD] age, 68.4 [9.6] years; 21 614 [47.4%] female) with advanced NSCLC were included in the study. PD-L1 testing increased from 468 (7.2%) in 2015 to 4202 (73.2%) in 2018. Within a subset of 7785 patients receiving first-line treatment in the period after first-line approval of pembrolizumab, those who received PD-L1 testing had a greater odds of receiving an ICI (odds ratio, 2.11; 95% CI, 1.89-2.36). Among patients with high PD-L1 expression (≥50%), 1541 (83.5%) received first-line ICI treatment; 776 patients (40.3%) with low PD-L1 expression (1%-49%) and 348 (32.3%) with negative PD-L1 expression (0%) also received ICIs. In addition, 755 untested patients (32.8%) were treated with a first-line ICI. The proportion of patients who received ICIs without PD-L1 testing increased during the study period (59 [17%] in quarter 4 of 2016 to 141 [53.8%] in quarter 4 of 2018). In this study, use of first-line ICI treatment increased among patients with advanced NSCLC with negative, low, or untested PD-L1 expression status in 2016 through 2018. These findings suggest that national practice was rapidly responsive to new clinical evidence rather than adhering to regulatory guidance in place at the time.
Highlights
The US Food and Drug Administration (FDA) first approved pembrolizumab, an immune checkpoint inhibitor (ICI) that targets programmed cell death 1 (PD-1), as first-line treatment for advanced non–small cell lung cancer (NSCLC) on October 24, 2016.1-3 This landmark approval was based on the results of a phase 3 randomized clinical trial including untreated patients with advanced NSCLC whose tumors highly expressed programmed cell death ligand 1 (PD-L1).[4]
In this study, use of first-line ICI treatment increased among patients with advanced NSCLC with negative, low, or untested PD-L1 expression status in 2016 through 2018
Adoption of PD-L1 Testing A total of 45 631 patients with advanced NSCLC were included in the study (Table 1)
Summary
The US Food and Drug Administration (FDA) first approved pembrolizumab, an immune checkpoint inhibitor (ICI) that targets programmed cell death 1 (PD-1), as first-line treatment for advanced non–small cell lung cancer (NSCLC) on October 24, 2016.1-3 This landmark approval was based on the results of a phase 3 randomized clinical trial including untreated patients with advanced NSCLC whose tumors highly expressed programmed cell death ligand 1 (PD-L1) (expression Ն50%).[4]. In the period after approval, evidence of clinical efficacy at lower PD-L1 expression levels emerged in a series of studies (eTable 1 in the Supplement),[4,5,6,7,8,9,10,11] leading to broadened approval without restriction to PD-L1 status. There was rapid adoption of pembrolizumab in the period after first-line approval, primarily among patients with high PD-L1 expression.[12] it remains unknown whether national practice subsequently reflected emerging clinical evidence (ie, first-line ICI treatment regardless of PD-L1 expression) vs the existing guidance that remained in place (ie, ICI treatment only in subsets of patients with PD-L1 expression). Whether ICIs were favored as monotherapy or in conjunction with other conventional therapies, such as cytotoxic chemotherapy, for patients with low or negative PD-L1 expression remains unexplored but may have implications for therapeutic efficacy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
