Impact of the Lung Immune Prognostic Index in non-small-cell lung cancer patients with PD-L1-low/negative tumors receiving chemoimmunotherapy: a real-world multicenter retrospective study.

[BACKGROUND] Chemoimmunotherapy has become one of the standard first-line treatment options for advanced non-small-cell lung cancer (NSCLC) across programmed death-ligand 1 (PD-L1) strata, yet outcomes in PD-L1-low/negative disease remain suboptimal. We evaluated whether the Lung Immune Prognostic Index (LIPI) at treatment initiation has prognostic value in this subgroup.

[PATIENTS AND METHODS] We conducted a multicenter retrospective cohort study across nine Japanese hospitals (January 2016-September 2021). Clinical data, including results of pretreatment blood tests at first-line treatment initiation, were collected and used to categorize LIPI (good, intermediate, or poor). Endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier and log-rank tests were used; prespecified multivariable Cox models were adjusted for LIPI (poor versus good/intermediate), PD-L1 tumor proportion score, Eastern Cooperative Oncology Group performance status, liver/brain metastases, treatment regimen, and age.

[RESULTS] We analyzed 176 patients (median age 71 years: PD-L1-low, 60.8%; PD-L1-negative, 39.2%). Median PFS and OS were 7.3 months [95% confidence interval (CI) 6.4-9.0 months] and 21.5 months (95% CI 15.4-24.6 months), respectively. Poor LIPI was associated with worse outcomes than good/intermediate LIPI (PFS: 3.6 versus 9.0 months, OS: 7.8 versus 23.9 months, both P < 0.001). In multivariable models, poor LIPI remained independently prognostic [PFS: adjusted hazard ratio (HR) 2.64, 95% CI 1.66-4.21; OS: adjusted HR 2.82, 95% CI 1.73-4.61].

[CONCLUSIONS] In first-line chemoimmunotherapy-treated PD-L1-low/negative NSCLC, baseline LIPI can be used to independently stratify PFS and OS and identify a subgroup with poor prognosis. LIPI may support risk stratification at first-line treatment initiation. Prospective studies are warranted to validate these findings and optimize personalized treatment approaches.