Real-world outcomes versus clinical trial results of first-line immunotherapy with or without chemotherapy in patients with metastatic non-small-cell lung cancer: the CORRELATE study.

[BACKGROUND] Recent data suggest that real-world overall survival (rwOS) and progression-free survival (rwPFS) in patients with metastatic non-small-cell lung cancer (mNSCLC) receiving first-line immunotherapy-based regimens are shorter than reported in randomized controlled trials (RCTs). This retrospective, observational study compared rwOS and rwPFS with outcomes observed in RCTs in patients with mNSCLC who received immunotherapy.

[PATIENTS AND METHODS] Eligible real-world (RW) patients from the United States Flatiron Enhanced Datamart had mNSCLC, started first-line treatment with an immunotherapy-based regimen between November 2016 and May 2021, and met key eligibility criteria per the registration RCTs for approved anti-programmed cell death (ligand) 1 [PD-(L)1]-based regimens: KEYNOTE-024, KEYNOTE-189, KEYNOTE-407, IMpower150, CheckMate 9LA, and CheckMate 227. rwOS and rwPFS were analyzed using the Kaplan-Meier method, per regimen/study cohort in subgroups by Eastern Cooperative Oncology Group (ECOG) performance status (PS; 0-1 or 2) and PD-L1 expression level (<1% or ≥1%). Efficacy-effectiveness factors (EEFs) quantified the gaps between RW and RCT outcomes.

[RESULTS] The analysis included 2705 and 661 patients with ECOG PS 0-1 and 2, respectively. Patients in the RW cohorts were older with a greater proportion of females compared with the corresponding RCTs. Among patients with PS 0-1, EEFs showed that median rwOS was 36%-61% shorter and median rwPFS was 21%-60% shorter compared with the reference RCTs. For the RW cohorts with sufficient sample size to permit analysis in patients with PS 2, this subgroup showed even greater differences in outcomes versus RCTs. In the RW KEYNOTE-189 and KEYNOTE-407 PS 0-1 cohorts, the PD-L1 ≥1% subgroup had numerically higher median rwOS and rwPFS than the PD-L1 <1% subgroup.

[CONCLUSIONS] PD-(L)1 inhibitors have been established as the standard-of-care first-line therapy in mNSCLC; however, in this study, RW survival outcomes were considerably shorter than those reported in RCTs. These findings highlight a potential unmet need for more effective treatment options for patients with mNSCLC in RW practice.