Chemoimmunotherapy Outcomes and Prognostic Factors in Patients with Advanced, Low PD-L1-Expressing Non-Small Cell Lung Cancer.

Chemoimmunotherapy is recommended for patients with non-small cell lung cancer (NSCLC) with low PD-L1 expression, but the effect of additional immunotherapy is heterogeneous in this population. To identify patients who do not benefit from the addition of immune checkpoint inhibitors (ICI) to chemotherapy, we conducted a retrospective study at 19 institutions in Japan. We analyzed 851 patients with advanced NSCLC with a PD-L1 tumor proportion score of 1% to 49% who received chemoimmunotherapy (n = 504) or chemotherapy (n = 347) between March 2017 and June 2022. After adjustment by propensity score matching, the median overall survival (OS) was 22.3 months in the chemoimmunotherapy group and 17.0 months in the chemotherapy-alone group (P = 0.01). Multivariate analysis showed that among 12 clinical factors, liver metastases (P = 0.001) and history of antibiotic use (P = 0.02) were independently associated with shorter OS in the chemoimmunotherapy group. Patients with liver metastases (OS, P = 0.4; progression-free survival, P = 0.06) or history of antimicrobial use (OS, P = 0.24; progression-free survival, P = 0.09) did not benefit from the addition of ICI to chemotherapy. Patients with a history of antimicrobial use experienced more severe pneumonitis with chemoimmunotherapy than all patients (P = 0.04). This cohort study showed that liver metastases and prior antimicrobial therapy are the most important clinical factors that attenuate the efficacy of chemoimmunotherapy in patients with low PD-L1 expression. SIGNIFICANCE: This study shows that liver metastases and prior antibiotic use are key factors for chemoimmunotherapy in advanced NSCLC cases with low PD-L1 expression. They reduce the benefit of adding ICIs to chemotherapy, underscoring the need for new strategies to improve ICI efficacy in patients.