First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for -altered NSCLC: a retrospective real-world POLISH study.

Background: There have been no comprehensive large-scale studies that have evaluated the benefits of chemotherapy-based regimens in addressing -altered advanced non-small-cell lung cancer (NSCLC) in a first-line setting. Data on alteration subtypes and concomitant alterations are also limited. Accordingly, our retrospective, real-world POLISH study assesses the efficacy of first-line chemotherapy alone (C) as well as combinations with immune checkpoint inhibitors (C + I) or angiogenesis inhibitors (C + A) for -altered NSCLC; molecular features are also reported.

Methods: -altered NSCLC patients who received a first-line treatment between November 2015 and September 2021 were screened. Patients treated with C, C + I, or C + A were included in our final efficacy analysis. Progression-free survival (PFS) was compared between the subgroups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to evaluate concomitant alterations.

Results: A total of 293 patients were screened, with an identification of amplification and 37 distinct mutations, and 210 cases treated with C, C + I, or C + A were ultimately included. C + A achieved longer PFS than C (5.63 4.03 months, hazard ratio: 0.64, 95% confidence interval [CI]: 0.46-0.88,  = 0.006). C + I did not improve median PFS compared to C + A or C (both  > 0.05), despite the programmed cell death ligand-1 (PD-L1) expression or tumor mutational burden. KEGG analysis revealed that concomitant upregulation of pathway signaling was common in -altered NSCLC.

Conclusion: Chemotherapy plus angiogenesis inhibitors may yield a greater survival benefit than chemotherapy alone in a first-line setting for -altered NSCLC, whereas an immune-based combination therapy may not be superior to a sole chemotherapy regimen. Activation of signaling may mediate immunosuppression in -altered NSCLC.