Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer

Abstract

Background: First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. Methods: Patients aged ≥18 years with confirmed advanced (stage III-IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. Results: Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3-11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3-12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8-12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4-15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. Conclusion: Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O-based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.

Real-world progression-free survival in first-line advanced non-small cell lung cancer treated with immunotherapy-based regimens using a US dataset

“…Real-world analyses can therefore identify subgroups of patients who may respond differently to specific therapeutic regimens. This supplementary data is supportive to the research article entitled “Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer” [1] . Using electronic health records data from a large demographically and geographically diverse oncology database, we present real-world progression-free survival (rwPFS) outcomes for patients with advanced non-small cell lung cancer in the United States treated with either first-line immunotherapy as monotherapy or single-agent immunotherapy combined with chemotherapy.…”

First-line immunotherapy in advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an International Expert Panel Meeting by the Italian Association of Thoracic Oncology

“…In this setting, no prospective data are available, and evidence is limited to few retrospective studies including both squamous and non-squamous histology and mixed populations. 35 , 36 Results from these studies were mainly limited to efficacy assessment. In the study by Waterhouse et al., 36 evaluating real-world outcomes of A-NSCLC patients receiving first-line ICIs, poor PS was confirmed as a negative prognostic factor in patients receiving combined chemotherapy plus immunotherapy (PS ≥2 patients: 16%; median OS 8 versus 11.6 months in squamous histology; 6.3 versus 14.2 months in non-squamous histology).…”

“… 35 , 36 Results from these studies were mainly limited to efficacy assessment. In the study by Waterhouse et al., 36 evaluating real-world outcomes of A-NSCLC patients receiving first-line ICIs, poor PS was confirmed as a negative prognostic factor in patients receiving combined chemotherapy plus immunotherapy (PS ≥2 patients: 16%; median OS 8 versus 11.6 months in squamous histology; 6.3 versus 14.2 months in non-squamous histology). 36 Similarly, a very recent study investigated the outcomes of trial-eligible and trial-ineligible patients treated with immunotherapy for different tumors.…”

“…A few retrospective reports included a poor PS population receiving chemotherapy plus immunotherapy combination; these confirmed the negative prognostic outcome of PS 2, in the absence of safety data evaluated. 35 , 36 …”

Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer

“…Though seemingly at odds with previously published randomized clinical trial (RCT) results, the duration of mOS observed on ICI therapy here is consistent with other real-world studies. [28][29][30] Moreover, it is worth noting that this is a summary result rather than a direct comparison between therapies, and could be due to the observational nature of this trial, the fact that patients were not randomized but rather therapy was decided by their physicians based on a multitude of factors including HIC results, 31 changes in treatment paradigms over the course of the study, and the inclusion of a heterogeneous real-world patient population often excluded from RCTs.…”