339P - Analysis of first- and second-line immunotherapy efficacy in metastatic non-small cell lung cancer with low PD-L1 expression

Background

Immune checkpoint inhibitors (ICI) improve overall survival (OS) in non-small cell lung cancer (NSCLC) but the efficacy of first- vs second-line ICI is unknown. We compared the outcomes of advanced NSCLC patients with <50% PD-L1 expression who received first- and second-line ICI.

Methods

This Australian-based retrospective cohort study included advanced NSCLC patients with PD-L1 <50% diagnosed between January 2016 and July 2021. All patients received either first- or second-line ICI. Patients with EGFR, ALK or ROS1 sensitising mutations were excluded. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). OS and PFS were estimated using Kaplan-Meier methods and Cox proportional-hazards models. Prognostic factors were tested using multivariate analyses.

Results

94 patients were eligible. 59% and 41% received first- and second-line ICI respectively. Baseline characteristics were: 56% PD-L1 <1%, 44% PD-L1 1-49%, 65% non-squamous, 66% male, 49% ECOG 0, 96% current/ex-smokers and 86% de-novo metastatic disease. 93% of those who received first-line ICI had concurrent chemotherapy. After a median follow-up of 14 months, there was no significant difference in OS in patients given first- vs second-line ICI (hazard ratio, HR OS 0.68, 95% CI 0.40-1.18, p = 0.17; median OS 16.0 vs 11.8 months). PFS and ORR were better in patients given first-line ICI (HR PFS 0.48, 95% CI 0.30-0.75, p = 0.01; median PFS 7.4 vs 4.2 months; ORR: 45.5% vs 15.4%). In patients aged 50-59 years, OS favoured first-line ICI (p = 0.009). Treatment-related AEs such as constipation/diarrhoea (55% vs 31%) and nausea/vomiting (42% vs 33%) were higher in first-line ICI. Rate of hospitalisations (56% vs. 51%) and immune-related AEs (24% vs. 28%) were similar in both groups.

Conclusions

In advanced NSCLC patients with <50% PD-L1 expression, there was a trend favouring OS in those who received first-line ICI but not statistically significant. However, PFS and ORR favoured first-line ICI. Higher rates of AEs should warrant caution.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.